Platelets metabolize arachidonic acid via cyclooxygenase and lipoxygenase (LO) enzymatic pathways. Although platelets produce large amounts of arachidonic acid metabolites via the LO pathway, little is known regarding the physiological significance of these products. We used three structurally dissimilar LO inhibitors, 5,8,11-eicosatriynoic acid (ETI), baicalein and phenidone, and found that LO inhibition attenuated thrombin- and U46619 (a thromboxane mimetic)-induced increases of platelet intracellular calcium ([Ca++]i) in washed human platelets. LO inhibitors also reduced platelet aggregation induced by thrombin and U46619. The effect of ETI on reducing the thrombin-induced [Ca++]i elevation persisted even when cation channels were blocked, suggesting that LO inhibitors modify release of Ca from intracellular stores. Stimulating endogenous LO product formation potentiated thrombin-induced [Ca++]i responses and aggregation, and these effects were eliminated by ETI. ETI did not alter inositol 1,4,5-trisphosphate production in stimulated platelets, but increased platelet cyclic AMP production in thrombin- or forskolin-stimulated platelets. These results suggest that LO products are regulators of platelet [Ca++]i mobilization and aggregation in response to some agonists, and that LO inhibitors may work in part by modifying platelet cyclic AMP metabolism.

Although PTH and PTH-related protein (PTHrP) are vasodilators, prolonged exposure to elevated levels of PTH is often associated with hypertension. We investigated the effects of prolonged incubation with PTH or PTHrP on arterial segments and cultured vascular smooth muscle cells (VSMC). PTH or PTHrP transiently relaxed precontracted arterial segments within 10 min. Additional PTH or PTHrP added after 40-min exposure to these peptides had little effect on vascular tone, whereas forskolin, isoproterenol, isobutylmethyl-xanthine, or acetylcholine were still potent. In fura 2-loaded VSMC, 5-min incubation with PTH or PTHrP attenuated angiotensin II (Ang II)-induced calcium mobilization, an effect that was reduced by preincubation of VSMC with PTH for 1.5 h. Similarly, 1.5-h preincubation with PTH or PTHrP decreased the cAMP response to these peptides but not to forskolin or NaF. Ang II potentiated the cAMP response to PTH and PTHrP but was also subject to desensitization. Nle8, 18Tyr34 bovine PTH(3-34) amide did not desensitize vascular tissue to PTH or PTHrP. Our results suggest that homologous desensitization to PTH or PTHrP in vascular tissue requires receptor stimulation, occurs proximal to G stimulatory protein, and impairs attenuation of calcium mobilization by PTH or PTHrP. This may be a mechanism by which vasodilator effects of these peptides are decreased with prolonged elevation of PTH levels.

Certain bioflavonoids and phenolic compounds have long been known to enhance catecholamine responses, in vivo and in vitro. In the present studies the flavone, baicalein, potentiated nerve-stimulated contractions in vitro in rat tail and femoral artery isometric ring preparations. Inhibition of catecholamine reuptake with cocaine or catecholamine metabolism with tropolone and parglyine (monoamine oxidase and catecholamine-O-methyl transferase inhibitors, respectively) did not alter baicalein's ability to potentiate contractile responses to nerve stimulation. Baicalein (10(-5) M), the prototype flavone, also increased sensitivity to exogenous norepinephrine, serotonin, arginine vasopressin and to the noncatecholamine alpha-1 and alpha-2 adrenergic agonists, cirazoline and tramazoline. Structure-function studies indicated that flavone potentiation required three contiguous A or B ring hydroxylations. Several nonflavone phenol derivatives with three contiguous hydroxyls also potentiated nerve stimulation responses. As baicalein is a potent lipoxygenase inhibitor, comparisons were made between potentiating ability and lipoxygenase inhibitory activity in a series of flavonoids. There was no direct correlation between inhibition of 12-hydroxy-5,8,10,14-eicosatetraenoic acid levels in thrombin stimulated human platelets and potentiation of contractile responses in the femoral artery. Additionally, the specific substrate analog lipoxygenase inhibitor, 5,8,11-eicosatriynoic acid, and the cyclooxygenase inhibitor, ibuprofen, were nonpotentiating. Ibuprofen pretreatment did not alter the potentiating action of baicalein. It is concluded that flavonoids with three contiguous hydroxyls on either the A or B ring increase in vitro vascular responsiveness via a post-synaptic process, independent of cyclooxygenase, lipoxygenase, monoamine oxidase or catecholamine-O-methyl transferase activity.

Plasma ionized calcium, platelet cytosolic calcium (using the fura-2 method in gel-filtered platelets), parathyroid hormone (both the intact hormone and a midmolecule portion), calcitriol, and calcidiol were measured in 19 untreated male patients with essential hypertension and 19 age-matched normotensive male research subjects. Mean levels of platelet cytosolic calcium, parathyroid hormone, calcitriol, and calcidiol were all significantly higher, whereas plasma ionized calcium was significantly lower, in the hypertensive group compared with the normotensive group. Both platelet cytosolic calcium and intact parathyroid hormone were positively correlated with mean arterial pressure (r = 0.58, p less than 0.001; r = 0.54, p less than 0.001, respectively), whereas plasma ionized calcium was inversely correlated with mean arterial pressure (r = -0.60, p less than 0.001) in the combined group of all study subjects. All three of these correlations were significant in the hypertensive group alone but not in the normotensive group alone. When analyzed with plasma ionized calcium, body mass index, serum calcitriol, and calcidiol in a multivariable regression model, the significance of the partial regressions of platelet cytosolic calcium and parathyroid hormone with mean arterial pressure persisted. Intact parathyroid hormone was positively correlated to platelet cytosolic calcium (r = 0.43, p less than 0.01) and plasma ionized calcium was inversely correlated to platelet cytosolic calcium (r = -0.44, p less than 0.01). These results confirm previous reports of disturbances of calcium metabolism in essential hypertension and suggest that the elevated platelet cytosolic calcium observed in essential hypertension may be linked to one or more of these alterations of calcium metabolism.

PURPOSE:There is increasing evidence of a central role for the calcium ion in blood pressure regulation. By studying blood pressure control in disorders of calcium homeostasis, a better understanding of the role of the calcium ion and certain calcitrophic hormones in modulating arterial pressure in humans may be gained. Our goal was to examine levels of blood pressure in a group of patients with either type Ia or type Ib pseudohypoparathyroidism (PsHP), a disorder characterized by target organ resistance to parathyroid hormone.PATIENTS AND METHODS:Forty-six patients with type I PsHP were recruited for the study (28 with type Ia and 18 with type Ib). Blood pressure was measured and the degree of obesity was assessed in all patients. Detailed measurements of hormones involved in blood pressure regulation were made in nine hypertensive patients with PsHP.RESULTS:Elevated arterial pressure was present in 18 of the 46 patients with PsHP, which comprised 53 percent (18 of 34) of the adult subjects. Prevalence of hypertension was similar in PsHP type Ia (nine of 21) and type Ib (nine of 13; p not significant) and was not related to coexisting hypothyroidism or degree of hypocalcemia. However, hypertension in PsHP was strongly linked to severe obesity. Mean body weights of normotensive and hypertensive patients with PsHP were 64 +/- 2.8 (SEM) kg (125 +/- 6 percent ideal body weight) and 96 +/- 4.7 kg (172 +/- 10 percent ideal body weight), respectively. Compared with obese hypertensive non-PsHP persons, hypertensive subjects with PsHP had reduced basal and posture-stimulated renin activity (basal, 1.68 +/- 0.36 [n = 9] versus 3.97 +/- 0.61 ng/ml/hour [n = 9] [p less than 0.05]; upright posture, 2.11 +/- 0.42 versus 7.13 ng/ml/hour [p less than 0.05]; and lower basal and posture-stimulated plasma norepinephrine levels (basal, 236 +/- 52 versus 426 +/- 37 pg/ml [p less than 0.05]; upright posture, 424 +/- 62 versus 707 +/- 64 pg/ml [p less than 0.05]).CONCLUSION:Our data suggest that hypertension is common in PsHP types Ia and Ib. This newly identified form of endocrine hypertension is strongly linked to excessive body weight but is associated with alterations in the renin-aldosterone and sympathetic nervous systems that are distinct from those encountered in obesity-related hypertension in the general population. The pathophysiologic basis for hypertension in these two distinctly different forms of PsHP remains to be determined.

Journal of the American Geriatrics SocietyVolume 36, Issue 9 p. 845-859 UCLA Geriatric Grand Rounds: Osteoporosis J. E. Morley Dr., Corresponding Author J. E. Morley Dr. From the Geriatric Research, Education and Clinical Center and Medical Service, VA Medical Center, Sepulveda, California 91343; and the Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024Director, GRECC, VA Medical Center (11E), 16111 Plummer St., Sepulveda, CA 91343Search for more papers by this authorM. J. Gorbien, M. J. Gorbien From the Geriatric Research, Education and Clinical Center and Medical Service, VA Medical Center, Sepulveda, California 91343; and the Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024Search for more papers by this authorA. D. Mooradian, A. D. Mooradian From the Geriatric Research, Education and Clinical Center and Medical Service, VA Medical Center, Sepulveda, California 91343; and the Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024Search for more papers by this authorA. J. Silver, A. J. Silver From the Geriatric Research, Education and Clinical Center and Medical Service, VA Medical Center, Sepulveda, California 91343; and the Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024Search for more papers by this authorA. S. Brickman, A. S. Brickman From the Geriatric Research, Education and Clinical Center and Medical Service, VA Medical Center, Sepulveda, California 91343; and the Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024Search for more papers by this authorF. E. Kaiser, F. E. Kaiser From the Geriatric Research, Education and Clinical Center and Medical Service, VA Medical Center, Sepulveda, California 91343; and the Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024Search for more papers by this author J. E. Morley Dr., Corresponding Author J. E. Morley Dr. From the Geriatric Research, Education and Clinical Center and Medical Service, VA Medical Center, Sepulveda, California 91343; and the Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024Director, GRECC, VA Medical Center (11E), 16111 Plummer St., Sepulveda, CA 91343Search for more papers by this authorM. J. Gorbien, M. J. Gorbien From the Geriatric Research, Education and Clinical Center and Medical Service, VA Medical Center, Sepulveda, California 91343; and the Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024Search for more papers by this authorA. D. Mooradian, A. D. Mooradian From the Geriatric Research, Education and Clinical Center and Medical Service, VA Medical Center, Sepulveda, California 91343; and the Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024Search for more papers by this authorA. J. Silver, A. J. Silver From the Geriatric Research, Education and Clinical Center and Medical Service, VA Medical Center, Sepulveda, California 91343; and the Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024Search for more papers by this authorA. S. Brickman, A. S. Brickman From the Geriatric Research, Education and Clinical Center and Medical Service, VA Medical Center, Sepulveda, California 91343; and the Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024Search for more papers by this authorF. E. Kaiser, F. E. Kaiser From the Geriatric Research, Education and Clinical Center and Medical Service, VA Medical Center, Sepulveda, California 91343; and the Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024Search for more papers by this author First published: September 1988 https://doi.org/10.1111/j.1532-5415.1988.tb04271.xCitations: 14Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat REFERENCES 1 Riggs BL, Melton LJ III: Involutional osteoporosis. 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The effect of a hypercalcemia-producing Leydig cell tumor on vascular reactivity in Fischer rats was studied. Seven to eight days after tumor implantation, there was no difference between tumor (T) and control (C) animals in serum calcium, serum phosphate, plasma catecholamine levels, mean arterial pressure (MAP), or blood pressure responses to norepinephrine (NE) infusion. At day 12–13 of tumor growth, the serum calcium in the tumor-bearing rats was significantly higher (12.2±0.8 vs. 9.7±0.3 mg%, P<.01) and their phosphate significantly lower (4.5±0.3 vs. 5.7±0.4 mg%, P<0.1 than controls. Plasma epinephrine (E) (497±154 vs. 62±13 pg/ml, P<.05), and norepinephrine (NE) (686±85 vs. 329±75 pg/ml, P<.01 were markedly elevated in the tumor rats. MAP and the blood pressure responses to graded NE infusions were significantly lower in tumor animals at Day 12–13, whereas there was no change in sensitivity to angiotensin II (AII) infusions. In vitro contractile responses of tail artery segments to transmural nerve stimulation (TNS) in animals with tumors were lower than in controls but there were no differences in sensitivity to exogenous NE in vitro. These results suggest that the tumor stimulates production of a circulating factor which desensitizes NE receptors and that this tumor also decreases neurovascular function by an undefined mechanism.

Some proposed mechanisms for the hypotensive effect of high calcium intake involve reduction in vascular responsivity. To assess the effect of dietary calcium on vascular responsivity, spontaneously hypertensive rats (SHR) were placed on normal (N-Ca; 0.4%) or high (H-Ca; 2.8%) casein-based synthetic diet for 4 wk. Intraarterial pressure, pressor response to graded intravenous infusion of norepinephrine (NE) and angiotensin II (ANG II), and in vitro vascular reactivity of tail artery segments to NE and transmural nerve stimulation (TNS) were studied. Urinary electrolyte excretion, plasma renin activity (PRA), aldosterone, NE, and epinephrine (EPI) were also determined. H-Ca SHR had a lower intraarterial systolic and diastolic pressure. However, H-Ca SHR had greater in vivo pressor response to both ANG II and NE. Maximal contractile force developed by tail artery segments in vitro in response to NE and TNS was slightly, but not significantly, higher in H-Ca SHR. In vitro dose-response curves to NE and TNS were not significantly different. Although H-Ca SHR had increased urinary excretion of sodium throughout the study period, PRA and aldosterone levels were similar in both groups. Plasma NE and EPI levels in the two groups were also not different. Despite lowered intra-arterial blood pressure, H-Ca SHR exhibited enhanced pressor response to ANG II and NE in vivo and a similar in vitro vascular reactivity to NE and TNS when compared with N-Ca SHR. Our results do not support a role for alterations in vascular reactivity to NE or ANG II in the hypotensive effect of high calcium intake in SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

ACTH-, angiotensin II (AII)-, and K+-mediated aldosterone responses in vitro are dependent on extracellular and intracellular Ca concentrations. This study examined in vivo the relationship of changes in ambient serum calcium (serum Ca) to ACTH- and AII-mediated aldosterone release in hypoparathyroid subjects. Plasma aldosterone (PA) responses to graded dose infusions of ACTH and AII were examined in hypoparathyroid (HypoPTH) patients before (n = 8) and after correction of hypocalcemia (n = 6) and compared to responses in 20 normotensive normocalcemic subjects. ACTH and AII were infused for 90 min at rates increasing from 12.5 to 50 mIU/30 min and 0.5 to 2.0 ng/kg X min, respectively. Pretreatment mean serum Ca was 6.8 +/- 0.2 (+/- SEM) mg/dl, and it rose to 9.3 +/- 0.2 mg/dl after 3-8 weeks of vitamin D administration. In the untreated HypoPTH patients, basal mean PA (5.4 +/- 1.3 ng/dl) was lower (P less than 0.01) than in the normal subjects (10.6 +/- 0.6 ng/dl) or treated HypoPTH patients (9.5 +/- 1.8 ng/dl). There was a marked reduction in PA responses to ACTH at all doses in the untreated HypoPTH patients compared to the normal subjects. With normalization of serum Ca in four patients, the mean peak PA response to ACTH (25.1 +/- 6.0 ng/dl) was not significantly different from normal (28.9 +/- 1.7 ng/dl). During graded dose AII infusion in five untreated HypoPTH patients, mean PA levels increased from 6.9 +/- 1.2 to 11.6 +/- 2.2 ng/dl; when the serum Ca was normal, the corresponding values were 8.7 +/- 1.8 and 20.2 +/- 3.61 ng/dl. There was a positive correlation (r = 0.475; P less than 0.05) between basal PA and serum Ca levels. In addition, maximum changes in mean arterial pressure in response to AII infusions were significantly greater after correction of hypocalcemia. These observations indicate that in HypoPTH patients, extracellular Ca concentrations can influence humoral aldosterone response to ACTH and AII and pressor responses to AII.

We studied Na transport in red blood cells (RBC) from six patients with hypoparathyroidism (HYPO; 3 postsurgical and 3 idiopathic) and 13 normal subjects. In HYPO, the effect of treatment-induced increases in serum Ca2+ on RBC Na transport also was examined. Na efflux mediated by the ouabain-sensitive Na,K pump and furosemide-sensitive Na,K cotransport (CoT) was examined by flux methodology in RBCs Na loaded to 5 levels of intracellular Na (Nai; 5-90 mM/liter cells) by the p-chloromercuribenzene method. The pump-mediated Na efflux was similar in untreated HYPO patients and normal subjects. Correction of hypocalcemia by vitamin D and oral calcium produced a mean increase in serum Ca2+ from 6.62 +/- 0.23 (+/- SEM) to 8.73 +/- 0.32 mg/dl. In HYPO patients treated with vitamin D and oral calcium, an increasing serum Ca2+ level was associated with significant (P less than 0.01) reductions in pump activity. Further, there was an inverse correlation (r = 0.813; P less than 0.001) between serum Ca2+ and pump-mediated Na efflux rate. RBC Na efflux through the CoT pathway was markedly reduced (P less than 0.05-0.01) in HYPO patients compared to normal subjects at all levels of Nai. Treatment-induced increases in serum Ca2+ had no effect on the reduced RBC CoT function in HYPO. Thus, changes in ambient serum Ca2+ can modulate the activity of the RBC Na,K pump in HYPO, with increases in Ca2+ inhibiting pump function. The markedly decreased RBC CoT activity was not related to associated hypertension or altered renal function and may represent a primary phenomenon in HYPO. These alterations in RBC Na transport may account for the higher Na, in RBCs of HYPO patients.

Single or graded doses of glucagon (Eli Lilly) were given to patients with pseudohypoparathyroidism (PsHP) type I to examine the possible presence of hormone resistance. The doses of glucagon ranged from 0.25-15 micrograms/kg. The following individuals were studied: 13 normal subjects, 5 patients with low erythrocyte N-protein activity (PsHP type Ia), and 7 patients with normal erythrocyte N-protein activity (PsHP type Ib). Two additional patients with treated primary hypothyroidism who were relatives of a patient with PsHP type Ib were also studied. The patients with PsHP type Ia had blunted plasma cAMP responses to all glucagon doses. In contrast, the patients with PsHP type Ib had normal cAMP responses to glucagon infusion. However, the 2 relatives of the patient with PsHP type Ib had clearly decreased cAMP responses to glucagon infusion; both had normal renal responses to PTH and were clinically and biochemically euthyroid at the time of study. Glucose responses to glucagon were normal in both PsHP groups; the glucose response per unit cAMP response was slightly, but not significantly, enhanced in PsHP type Ia patients. Glucagon resistance appears to be a common finding in patients with PsHP type Ia, but not in those with PsHP type Ib. However, the observation of reduced glucagon responsivity in association with familial hypothyroidism in a kindred with PsHP type Ib suggests the possibility that this disorder may also cause disturbances in several hormone systems.

The lipolytic response to isoproterenol infusion was examined in seven normal subjects and six patients with pseudohypoparathyroidism type I [two had deficiency of the hormone receptor-cyclase coupling protein (N-protein) and four did not]. Despite blunted plasma cAMP responses to isoproterenol in both subgroups of pseudohypoparathyroidism patients, the serum FFA responses were normal. We conclude that changes in plasma cAMP do not reflect the adequacy of the lipolytic response to isoproterenol.

We evaluated the effects of chronic massive elevations of serum GH and PRL on calcium metabolism in rats bearing the MStT/W15 and 7315a transplantable pituitary tumors. MStT/W15 tumor rats manifest elevated serum GH and PRL levels, hypercalcemia, hypercalciuria, and elevated serum levels of PTH and 1,25-dihydroxyvitamin D. The hypercalcemia was not reversed by dexamethasone or propranolol treatment, but was ameliorated by starvation. Parathyroidectomy produced hypocalcemia in the MStT/W15 tumor rats, confirming the parathyroid dependence of the hypercalcemia. The 7315a tumor produced a milder degree of hypercalcemia, along with elevated serum levels of PRL, ACTH, and corticosterone; serum GH was normal. In high concentrations, PRL and/or GH may stimulate the secretion of PTH as well as enhance dietary calcium absorption, in part through the mediation of 1,25-dihydroxyvitamin D.

Alterations in red blood cell (RBC) Na+,K+ pump and in Na+,K+ cotransport (CoT) have been described in essential hypertension (EH). We examined pump and CoT in 50 normotensive (NT) subjects and 58 EH subjects subdivided by race and family history of hypertension (+ FH). RBCs were preloaded with Na+ to obtain intracellular levels of 25 mM/liter cells by using the p-chloromercuribenzene sulfonic acid (pCMBS) method. Na+ and K+ efflux rates into a magnesium-sucrose medium were quantitated in the presence of ouabain and ouabain plus furosemide to define pump and CoT activity respectively. Mean intracellular Na+ content was higher (p less than 0.05) in black NT and HT subjects compared to Caucasians. Mean RBC CoT was lower in black EH compared to NT and compared to Caucasian NT and HT subjects. Conversely, Caucasian HT patients had higher mean CoT than NT subjects. Subdivision into + FH revealed very little effect of + FH on CoT in black NT and HT subjects. In Caucasian NT and HT subjects with + FH, mean CoT was significantly reduced (less than 0.3 mM/liter cells/hr) compared to those without + FH. A subgroup of Caucasian EH subjects displayed high CoT (greater than 0.6 mM/liter cells/hr); a + FH had little impact on the high CoT group. There was no correlation between RBC CoT activity and age, sex, severity of hypertension, urinary sodium excretion, and plasma aldosterone. There was a positive correlation (r = + 0.47; p less than 0.01) between CoT and upright plasma renin activity.(ABSTRACT TRUNCATED AT 250 WORDS)

We have developed a method for the measurement of 1,25-dihydroxyvitamin D [1,25-(OH)2D] which is based on the selective internalization and subsequent binding of 1,25-(OH)2D to its specific receptor inside cultured target cells. This technique provides the means of assaying 1,25-(OH)2D directly in blood extracts without prior biochemical isolation of this hormone from other metabolites of vitamin D. The displacement of 1,25-(OH)2-[3H]D3 bound to the intracellular receptor by the extracted 1,25-(OH)2D provides a measurement of its concentration in the blood samples. The method is sensitive to 2 pg/tube and can be performed with 1- to 2-ml samples. The intra- and interassay coefficients of variation are 10.2% and 15.3%, respectively. Other major metabolites of vitamin D, at their circulating levels, do not interfere with the 1,25-(OH)2D measurement. Moreover, 1,25-(OH)2D levels determined by this direct method correlate closely (r = 0.93) with the values determined by the traditional high pressure liquid chromatographic assays on the same samples. Using the cytoreceptor assay we found that normal adults (n = 79) had a mean (±SD) 1,25-(OH)2D level of 33.8 10.64 pg/ml; normal children (n = 40) had higher 1,25-(OH)2D levels than the adults (P < 0.0005), with a mean level of 43.3 ± 13.9 pg/ml. In normals subjects, 1,25-(OH)2D levels correlated negatively with age (r = −0.40; P < 0.001). Pregnant women (n = 6) in the third trimester had elevated levels, with a mean of 96.5 ± 17.1, anephric patients (n = 3) had undetectable levels, and patients on hemodialysis (n = 11) had a mean of 11.5 ± 6.7 pg/ml, significantly (P < 0.0005) lower than normal. Adult patients with primary hyperparathyroidism (n = 25) had a mean 1,25-(OH)2D level of 50.2 ± 15.3 pg/ml, significantly (P < 0.0005) higher than normal; in this group, hormone levels correlated positively with calcium absorption (r = 0.81; P < 0.001) and serum calcium (r = 0.53; P < 0.02 and negatively with serum phosphate (r = −0.49; P < 0.05). (J Clin Endocrinol Metab56: 751,1983)

Plasma cAMP, serum glucose, and cardiovascular responses to isoproterenol infusion were examined in seven normal subjects and seven patients with pseudohypoparathyroidism (PHP), type I (three with deficiency of the hormone receptor-cyclase coupling protein (N-protein) and four who were N-protein replete). Although plasma cAMP responses were blunted in both subgroups of PHP patients, the cardiovascular and glucose responses to isoproterenol were normal. We conclude that the blunted plasma cAMP response to isoproterenol in PHP does not depend on deficient N-protein coupling of adenylate cyclase to the beta-adrenergic receptor and that the cardiovascular and glucose responses to isoproterenol are not reflected in changes in plasma cAMP.

The relationship between 24-h recumbent blood pressure levels and secretory patterns of catecholamines was investigated in 4 patients with pseudohypoparathyroidism (PsHP) and hypertension and in 9 patients with essential hypertension. A clear circadian rhythm of blood pressure and catecholamines was documented in both groups with lowest levels of blood pressures and catecholamines occurring during sleep. During the 24-h period of recumbency mean arterial blood pressure (MAP) was correlated (r = 0.63, p less than or equal to 0.01) with plasma norepinephrine (N) in the patients with essential hypertension, but this correlation was weaker in patients with PsHP (r = 0.38, p less than or equal to 0.05). MAP was more closely related to plasma epinephrine (E) (r = 0.62, p less than or equal to 0.01) than to plasma NE in patients with PsHP. Plasma NE and E levels were considerably lower in patients with PsHP than in patients with essential hypertension throughout the 24-h recumbent period. The sleep-related decline in blood pressure and NE was less than in patients with essential hypertension. These results suggest that while the sympathetic nervous system may have a role in hour-to-hour maintenance of blood pressure in patients with PsHP and hypertension, it does not appear to be responsible for the elevated arterial pressure in these patients. Factors other than those investigated, such as obesity, alterations in sodium homeostasis of refractoriness of the vascular smooth muscle to the vasodilatory effect of PTH may be involved in the pathogenesis of hypertension in PsHP.

To evaluate the relationship between aluminum and the characteristics of bone disease in uremia, bone aluminum content and quantitative histomorphometric analysis of bone were evaluated in bone biopsies from 59 uremic patients undergoing maintenance hemodialysis. Biopsies were classified as showing 1) pure osteomalacia (OM) in 23 cases, 2) osteitis fibrosa (OF) in 13, 3) mixed in 7, and 4) mild lesions in 16. There were no significant differences in levels of serum calcium or alkaline phosphatase between the groups, but serum phosphorus levels were slightly higher in those with OF. Serum immunoreactive parathyroid hormone levels were greater in the patients with OF and mixed lesions than in patients with OM or mild lesions (P less than 0.01). Bone aluminum exceeded normal in all groups (P less than 0.01), with values of 175 +/- 18 mg/kg dry wt in OM patients, 46 +/- 7 of OF patients, 81 +/- 29 in mixed subjects, and 67 +/- 7 in patients with mild lesions. Bone aluminum was significantly higher in the OM patients than in any other group (P less than 0.01); also, bone aluminum correlated with the quantitative measure of unmineralized osteoid in OM (r = 0.67; P less than 0.001); no correlations existed for the other groups. There were inverse correlations between bone aluminum and the serum immunoreactive parathyroid hormone (r = -0.35; P less than 0.01) and resorbing surface on biopsy (r = -0.44; P less than 0.001). Bone aluminum correlated with the duration of hemodialysis in patients with OF with mixed and mild lesions (r = 0.49); no relation was seen in OM patients, and bone aluminum was higher for the duration of dialysis, suggesting that aluminum may accumulate more rapidly in OM subjects. These findings are consistent with but do not prove the hypothesis that aluminum plays a pathogenic role in dialysis osteomalacia; the mechanism by which aluminum accumulates remains unknown.