Patients with high blood pressure tend to be insulin resistant, glucose intolerant, hyperinsulinemic, and dyslipidemic. Since these metabolic defects are accentuated by obesity, we thought it important to compare the effects of 3 months' treatment with either lisinopril (20 mg/day) or low dose hydrochlorothiazide (12.5 mg/day) on blood pressure and glucose, insulin, and lipoprotein metabolism in obese patients with hypertension. There were 14 patients in each group, and they were similar (mean +/- SE) in age (54 +/- 3 v 50 +/- 4 years), gender (nine men/five women), and body mass index (33.4 +/- 0.8 v 33.9 +/- 0.9 kg/m2). Patients treated with lisinopril had a somewhat greater fall in both systolic (18 +/- 3 v 10 +/- 3 mm Hg) and diastolic (12 +/- 2 v 8 +/- 1 mm Hg) blood pressure, but only the change in systolic pressure was statistically significant (P < .05). Plasma glucose, insulin, and triglyceride concentrations were measured at hourly intervals from 8 AM to 4 PM (breakfast at 8 AM and lunch at 12 PM), and there was a modest increase in all three variables following hydrochlorothiazide treatment (P < .05 to P < .09). However, daylong plasma glucose, insulin, and triglyceride concentration did not change with lisinopril treatment. Finally, neither the ability of insulin to mediate glucose disposal nor fasting lipid and lipoprotein concentrations, changed with either treatment. In conclusion blood pressure decreased significantly following treatment with either lisinopril (20 mg/day) or hydrochlorothiazide (12.5 mg/day).(ABSTRACT TRUNCATED AT 250 WORDS)

Resistance to insulin-mediated glucose disposal has been previously shown to be increased in association with obesity, high blood pressure, and non-insulin-dependent diabetes mellitus. We initiated the present study to quantify the separate effects of hypertension and non-insulin-dependent diabetes mellitus on insulin resistance in both nonobese and obese subjects. To accomplish this, 88 subjects were divided into the following five experimental groups: normal blood pressure, nonobese (n = 17); normal blood pressure, obese (n = 18); high blood pressure, nonobese (n = 18); high blood pressure, obese (n = 19); and high blood pressure, obese, non-insulin-dependent diabetes mellitus (n = 16). Plasma glucose and insulin concentrations were measured before and after a 75-g oral glucose load. Resistance to insulin-mediated glucose disposal was estimated by determining the steady-state plasma insulin and glucose concentrations during the last 30 minutes of a continuous infusion of somatostatin (5 micrograms/min), exogenous insulin (25 mU/m2 per minute), and glucose (240 mg/m2 per minute). Since the steady-state plasma insulin concentrations are similar in all subjects, the higher the steady-state plasma glucose, the more insulin resistant the individual. Nonobese subjects with normal blood pressure had the lowest plasma glucose and insulin responses and steady-state plasma glucose concentrations, and their values were significantly different from the other four groups. Obese or nonobese subjects with high blood pressure had significantly higher plasma glucose responses and steady-state plasma glucose concentrations than did their respective weight-matched control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirty patients with hypertension were enrolled in this study, 13 had non-insulin-dependent diabetes mellitus (NIDDM) and 17 were nondiabetic. Patients were treated with doxazosin for approximately 4 months, and blood pressure fell significantly (P < .001) in both nondiabetics (149/96 to 134/85 mm Hg) and in those with NIDDM (154/96 to 143/84 mm Hg). In the nondiabetic group, doxazosin treatment was associated with significant improvement in insulin-mediated glucose disposal (P < .05) and lower plasma insulin (P < .001), and triglyceride (P < .001) concentrations measured at hourly intervals from 8 AM to 4 PM (breakfast at 8 AM and lunch at noon). In addition, fasting total plasma (P < .001) and VLDL cholesterol (P < .01), and total plasma (P < .05), VLDL (P < .08), LDL (P < .01), HDL (P < .01) triglyceride concentrations were lower following doxazosin treatments in the nondiabetic group, as was the ratio of total to HDL cholesterol (P < .001). Finally, apoprotein B concentrations fell with doxazosin in the nondiabetic group (P < .01). Significant changes seen in the group with NIDDM included a decrease in the ratio of total to HDL cholesterol (P < .001) and a fall in apoprotein B concentration (P < .05). However, values for all other variables did not change significantly with treatment in this group. Thus, doxazosin treatment of nondiabetic subjects with high blood pressure was associated with a series of changes in glucose, insulin, and lipoprotein metabolism that should decrease risk of coronary heart disease (CHD) in these individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of atrial natriuretic hormone (ANH) on metoclopramide-induced stimulation of aldosterone was studied in eight healthy young men after 3 days of controlled diet (150 mEq sodium, 100 mEq potassium). Baseline values were obtained after subjects had remained sitting for 1 hour. Subjects then received 2-hour infusions of placebo, dopamine (2 micrograms/kg/min), ANH (0.6 pmol/kg/min), and ANH plus dopamine. One hour after the beginning of each infusion, a 10 mg intravenous bolus of metoclopramide was given. Prolactin levels increased 10-fold after metoclopramide with placebo infusion, and about 50% of this stimulation was abolished by preinfusion with dopamine. ANH preinfusion did not suppress prolactin release. Urinary sodium excretion increased prominently during dopamine infusion. ANH at this dose had no effect on natriuresis. The dopamine dose given had almost no effect on metoclopramide-induced aldosterone secretion, whereas ANH infusions, which resulted in approximate doubling of plasma ANH levels, suppressed aldosterone. This study supports a role of ANH in aldosterone regulation, even at nonnatriuretic doses, and suggests that ANH is acting not only through the renin-angiotensin system but under certain conditions has significant physiologic action directly on glomerulosa cells.

Various facets of glucose, insulin, and lipid metabolism were compared in 76 normal volunteers--38 with and 38 without a family history of hypertension. The two groups were comparable in terms of age, gender distribution, and degree of obesity (both generalized and abdominal). Although the plasma glucose response to oral glucose was similar in both groups, glucose-stimulated insulin concentrations were significantly greater in volunteers with a family history of hypertension (P < .001). Furthermore, the steady state plasma glucose concentration during a constant infusion of glucose, insulin and somatostatin was significantly greater in subjects with a family history of hypertension (8.1 +/- 0.6 v 6.2 +/- 0.6 mmol/L, P < .001). Since the steady-state plasma insulin levels during the infusion were similar, these results indicate that normotensive individuals with a family history of hypertension are relatively insulin resistant. Finally, plasma very low density lipoprotein (VLDL) triglyceride and VLDL cholesterol were higher in those with a family history of hypertension, as was the ratio of total to high density lipoprotein cholesterol. Thus, normotensive individuals with a family history of high blood pressure are insulin resistant, hyperinsulinemic and dyslipidemic when compared to a matched group of healthy volunteers without a family history of hypertension.

Regulation of atrial natriuretic hormone (ANH) receptor binding and aldosterone suppression was studied in isolated adrenal glomerulosa cells from rats fed a high-salt (HS) or low-salt (LS) diet for 3 days. In plasma of HS rats, aldosterone levels were 5 times lower and immunoreactive ANH two times higher than in LS rats. Competitive binding studies showed the same affinity for human atrial natriuretic hormone (hANH) in both pools of cells, but receptor density was 50% higher on LS cells. A linear ANH analog that binds to non-guanylate-cyclase-coupled receptors did not show increased binding to LS cells. Cyclic GMP production in response to hANH was identical in both groups. The aldosterone-inhibitory effect of hANH on both groups of basal and angiotensin II-stimulated cells was also identical. Thus a short-term high-salt diet causes decreased density of ANH receptors in glomerulosa cells without changing biological activity of ANH. These results suggest that dietary salt content changes the number of ANH receptors and that non-guanylate-cyclase-coupled receptors contain at least two classes of receptors.

To further assess the mechanism of atrial natriuretic hormone (ANH) induced suppression of aldosterone, we infused 0.5 pmol/kg/min Ser-Tyr28 human ANH over 2 h under three dietary conditions: low salt (LS), low potassium (LK), and high potassium (HK). The diets were consumed for 3 days before each study day.After 3 days of LK diet, blood pressure was slightly higher than under the other conditions. Serum potassium on LK was significantly lower than on HK (3.8 +/- 0.1 upsilon 4.3 +/- 0.2). The ANH infusion did not cause any changes in blood pressure or urinary sodium and potassium excretion. Urine volume increased with ANH infusion under all diet conditions. Plasma renin activity and plasma angiotensin II levels were significantly lower on LK than on LS or HK, probably reflecting sodium retention. Increase in plasma ANH levels of about 75% (well within normal range) suppressed all hormonal parameters on LS and HK diets, but had no significant effect on LK diet. The pattern of aldosterone changes closely followed the changes in the renin-angiotensin system. We conclude that under various physiologic conditions ANH suppresses aldosterone predominantly through suppression of renin.

To investigate the mechanisms by which small changes in plasma levels of atrial natriuretic hormone (ANH) affect aldosterone, 10 normal young men were infused for 2 h with 0.6 pmol/kg.min human [Ser,Tyr28]ANH under 3 study conditions: 1) high salt diet (H), 2) low salt diet (L), and 3) low salt diet plus pretreatment with the angiotensin-converting enzyme inhibitor enalapril (LE). Baseline ANH levels were higher on H than on L or LE. A postural drop in ANH was observed when subjects went from standing to sitting. Plasma ANH levels increased during infusion by up to 4.5 pmol/L (H, 7.0 +/- 1.3 to 11.5 +/- 1.4; L, 4.3 +/- 0.6 to 8.7 +/- 1.1; LE, 4.2 +/- 0.5 to 8.6 +/- 1.5). At all time points, plasma ANH was well within the normal range. Plasma aldosterone did not change during H, decreased by about 60% for both low salt conditions, and remained suppressed at 1 h of recovery for L, but not for LE. This suggests that ANH can suppress aldosterone by both indirect and direct mechanisms, although the indirect mechanism appears to predominate. A prompt increase in urine flow was seen during ANH infusion and was sustained at 1 h of recovery, but little change was seen in urinary sodium or potassium excretion, heart rate, or blood pressure. The difference between the natriuretic and diuretic effects of ANH was seen under all conditions. These results support the hypothesis that within the normal physiological range, ANH is a regulator of salt and water metabolism in normal man.