Background: Intracranial haemorrhage (ICH) is the type of stroke associated with the highest death rate, and about 30% of ICH occurs in patients on antithrombotic treatment. This study relates clinical presentations and outcome of ICH patients on oral anticoagulant (OA) or antiplatelet (AP) therapy admitted to 33 Italian emergency departments (ED). Methods: Consecutive patients were enrolled after cranial computed tomography (CT). Primary outcome was the Modified Rankin Scale (MRS) score at 3 months of follow-up. Common descriptive statistics were computed after stratification for traumatic or spontaneous ICH and identification of the anatomical location of bleeding. Multivariate logistic regression was used to assess predictors of death. Results: We recruited 434 patients on AP therapy and 232 on OA. There were 432 spontaneous and 234 traumatic ICH patients. The proportions of AP and OA patients undergoing neurosurgery were 21.8and 19.4%, respectively, while <30% underwent procoagulant medical treatment. At the 3-month follow-up, the case fatality rate was 42.0%, while disability or death (MRS 3–6) was 68.1%. The odds ratio for death in OA versus AP patients was 2.63 (95% CI 1.73–4.00) in the whole population and 2.80 (95% CI 1.77–4.41) in intraparenchymal event patients. Glasgow Coma Scale, age, spontaneous event and anticoagulant use were found to be predictors of death both in traumatic and spontaneous events. Conclusion: This study confirms the high prevalence of death or disability in OA and AP patients with ICH. As far as the determinants of mortality and disability are concerned, the results of this study might be useful in the clinical management and allocation of resources in the ED setting. The observed low use of procoagulant therapy highlights the need for ED educational programmes to heighten the awareness of available and effective haemostatic treatments.

Objective The aim of this study was to compare the time-effect profiles of a once-daily administration of valsartan and amlodipine, each given alone or in combination with hydrochlorothiazide, in terms of ambulatory blood pressure (BP) and heart rate in elderly patients with isolated systolic hypertension.Methods One hundred and sixty-four elderly outpatients with systolic hypertension received valsartan 80 mg (n = 79) or amlodipine 5 mg (n = 85) once daily for eight weeks, after which the patients with poorly controlled office BP were up-titrated to valsartan 160 mg or amlodipine 10mg once daily. If their office systolic BP was still > 140 mmHg after eight weeks at these doses, 12.5 mg hydrochlorothiazide was added for a further eight weeks. The hourly BP decreases in all of the patients were calculated on the basis of 24-h ambulatory recordings made after the placebo period and at the end of active treatment The trough/peak ratio and smoothness index were calculated in the responders.Results Both the valsartan- and amlodipine-based treatments effectively lowered mean 24-h, daytime and night-time systolic ambulatory BID (all p<0.001) without any significant differences between the two regimens. Ambulatory heart rate decreased in the subjects on valsartan and slightly increased in those on amlodipine (the differences in 24-h and daytime heart rate were significant (p=0.008 and 0.002 respectively). Among the 138 responders, the valsartan-based treatment had a greater anti-hypertensive effect during the daytime hours (p=0.02), a difference that was also significant for average 24-h BID (p=0.02). The mean systolic BP trough/peak ratio was 0.56 in the patients on valsartan, and 0.77 in those on amlodipine (NS). The smoothness index was respectively 1.70 and 1.58 (NS).Conclusions The present results show that both the valsartan- and amlodipine-based treatments lead to a similar long-term reduction in 24-h systolic BR However, in treatment responders, valsartan has a greater anti-hypertensive effect during the daytime. (C) 2004 Lippincott Williams Wilkins.

Background: The goal of antihypertensive therapy is to provide good blood pressure (BP) control without eliciting adverse effects.Objective: This stud), compared the risk-benefit profile of the angiotensin 11 receptor blocker valsartan with that of the angiotensin-converting enzyme inhibitor lisinopril in patients with mild to severe hypertension. The primary objective was to show that the equipotent BP-lowering effect of the valsartan-based treatment is accompanied by a better tolerability profile.Methods: This 16-week, randomized, double-blind, parallel-group study was conducted at 88 outpatient centers across Italy After a 2-week placebo run-in period, patients aged ! IS years with mild to severe hypertension (systolic BP [SBP], 160-220 mm Hg; diastolic BP [DBP], 95-110 mm Hg) were eligible. Patients were randomized to receive once-daily, oral, self-administered treatment with valsartan 160-mg capsules or lisinopril 20-mg capsules under double-blind conditions for 4 weeks. Responders continued monotherapy, whereas nonresponders had hydrochlorothiazide 12.5 mg added for the final 12 weeks of the study The 2 primary variables used to assess the equivalence of therapeutic efficacy of the 2 regimens were sitting SBP and sitting DBP, which were measured at weeks 0 (baseline), 4, 8, and 16. The rate of drug-related adverse events (AEs) was used to assess whether I treatment had a better tolerability profile than the other. Tolerability was assessed by collecting information about AEs by means of questioning the patient or physical examination at each visit.Results: A total of 1213 patients were enrolled (635 men, 578 women; mean [SD] age, 54.5 [10.1] years [range, 28-78 years]). The study was completed by 1100 patients (553 receiving valsartan and 547 receiving lisinopril). Fifty-one patients (8.4%) treated with valsartan and 62 (1.2%) treated with lisinopril withdrew, mainly because of AEs (9 [1.5%] and 23 patients [3.8%], respectively). The valsartan- and lisinopril-based treatments were similarly effective in reducing sitting BP with mean SBP/DBP reductions of 31.2/15.9 mm Hg and 31.4/15.9 mm Hg, respectively At the end of the study, BP was controlled in 82.7% of the patients receiving valsartan and 81.6% of those receiving lisinopril. AEs were experienced by 5.1% of the patients treated with valsartan and 10.7% of those treated with lisinopril (P = 0.001), with dry cough observed in 1.0% and 7.2% of patients, respectively (P < 0.001).Conclusions: Valsartan and lisinopril were both highly effective in controlling BP in these patients with mild to severe hypertension, but valsartan was associated with a significantly reduced risk for AEs, especially cough. (C) 2004 Excerpta Medica, Inc.

The present study was designed to evaluate the effect of combination therapy using the angiotensin-converting enzyme-inhibitor lisinopril and the dihydropyridine calcium antagonist nifedipine GITS on the degree and homogeneity of 24-hour blood pressure reduction in essential hypertensive patients. After a 4-week placebo run-in period, 51 patients (mean age, 54.4 ± 9.4 years) with essential hypertension and clinic diastolic blood pressure between 105 and 115 mm Hg were randomized to 4-week treatment with lisinopril (20 mg), nifedipine GITS (30 mg), or their combination according to a multicenter, randomized, double-blind, crossover study. Trough clinic blood pressure and 24-hour ambulatory blood pressure were measured at the end of the run-in period and after 4 weeks of treatment. In addition to clinic and 24-hour average blood pressure reduction, the trough-to-peak ratio and the smoothness index, a new measure for the homogeneity of blood pressure reduction, were also calculated. Although both lisinopril and nifedipine GITS produced a significant reduction in clinic and 24-hour average blood pressure values, the reduction obtained with the combination was significantly (P < 0.001) greater. Moreover, the combination therapy increased (P < 0.01) the smoothness index as compared with each single drug for both systolic (lisinopril, 1.02; nifedipine GITS, 1.1; combination, 1.76) and diastolic (lisinopril, 0.98; nifedipine GITS, 0.87; combination, 1.54) blood pressure values, whereas trough-to-peak ratio values (expressed as median) for systolic (lisinopril, 0.41; nifedipine GITS, 0.52; combination, 0.55) and diastolic (lisinopril, 0.35; nifedipine GITS, 0.40; combination, 0.49) blood pressure values were not significantly increased by the combination therapy. Thus, antihypertensive treatment with the combination of lisinopril and nifedipine GITS is more effective and balanced over the 24 hours than the combination components administered alone, confirming that the smoothness index is superior to the trough-to-peak ratio in assessing homogeneity of pharmacologic blood pressure reduction.

Objective Marked alterations have been demonstrated to occur in the platelet α2-adrenoceptors of patients with essential hypertension. The purpose of this study was to determine whether antihypertensive treatment with α-adrenergic blocker doxazosin or β-adrenergic blocker propranolol can affect the af(r)nity and the density of platelet α2-adrenoceptors in such patients. Subjects and methods In two groups of 22 previously untreated, essential hypertensive patients, the mean affinity (Kd) and density (Bmax) of platelet α2-adrenoceptors were studied by [3H]-UK 14304 binding assays; the first assays were performed before any medication was begun, the second were performed after treatment for up to 13 weeks with doxazosin or propranolol. A third group of 22 healthy normotensive volunteers matched by age, sex and body mass index was used as control. Results Blood pressure did not differ significantly in the two hypertensive groups, and treatment with the two drugs resulted in closely similar, normal blood pressure levels. Kd and Bmax values were significantly higher in the two hypertensive groups than in controls. After treatment with propranolol the binding parameters did not change significantly, whereas after treatment with doxazosin Kd and Bmax returned to normotensive values. Conclusions In previously untreated, essential hypertensive patients platelet α2-adrenoceptors have a lower affinity but a higher density than in normotensive subjects. Despite similar effects on blood pressure, the treatment with the α2-adrenergic blocker doxazosin is followed by restoration of normal findings in the binding assays of platelet α2-adrenoceptors whereas the treatment with the β-adrenergic blocker propranolol does not alter the Kd and Bmax values.

AIMS:The purpose of this study was to determine whether human platelet alpha2-adrenoceptors were altered in essential hypertension. A systematic analysis was carried out on 165 normotensives and 124 untreated primary hypertensives.METHODS:The study was performed at different levels: i) density and affinity of platelet alpha2-adrenoceptors were determined by receptor binding assays using the full alpha2-adrenoceptor agonist [3H]-UK 14304 and a thermodynamic analysis of data was carried out to evaluate if binding mechanisms at the molecular level were altered during hypertension; ii) the functionality of Gi proteins coupled to alpha2-adrenoceptors and iii) forskolin-stimulated cAMP levels were measured.RESULTS:Platelet alpha2-adrenoceptors mean density (Bmax) and affinity (Kd) (+/-s.e.mean) were significantly lower and higher, respectively, in normotensive than in hypertensive subjects [Bmax=327+/-4 vs 435+/-5 fmol mg(-1) of protein (P<0.01) and Kd=3.76+/-10.05 vs 6.50+/-0.15 nM (P<0.01), respectively]. The 50% stimulating concentration of adrenaline on [35S]-GTPgammaS binding to Gi proteins was significantly (P<0.01) lower in normotensives (12+/-2 nM) than in hypertensives (110+/-10 nM). The 50% inhibiting concentration of adrenaline on forskolin-stimulated cAMP levels was significantly (P<0.01) lower in normotensive (22+/-2 nM) than in hypertensive subjects (200+/-25 nM).CONCLUSIONS:Present analysis, including receptorial and functional data, provides evidence that marked alterations occur in platelet alpha2-adrenoceptors of hypertensive subjects.

This study was performed to determine whether the stimulatory effect of plasma angiotensin II (ANG II) on arginine vasopressin (AVP) and oxytocin (OT) secretion in humans is mediated by AT1 subtype receptors. For this purpose, the effects of the AT1 receptor antagonist losartan (50 mg orally) or a placebo on the AVP and OT responses to ANG II (intravenous infusion for 60 minutes of successively increasing doses of 4, 8, and 16 ng/kg min; each dose for 20 minutes) administration were evaluated in seven normal men. In additional experiments, the same subjects were tested with losartan (50 mg orally) alone or placebo alone. Neither losartan nor placebo given alone modified the basal levels of AVP and OT. ANG II infusion induced significant increments in both serum AVP and OT levels (mean peaks were 1.55 and 1.41 times higher than baseline, respectively). Both hormonal responses to ANG II were completely abolished by pretreatment with losartan. These data provide evidence of AT1 receptor involvement in mediation of the ANG II-stimulating effect on AVP and OT secretion.

OBJECTIVES:Arginine-vasopressin (AVP) and oxytocin (OT) secretions are abnormally stimulated by hypoglycaemia in patients with IDDM. Since previous studies showed that AVP secretion is influenced by the persistence of residual endogenous insulin secretion, we wondered whether this factor also regulates OT secretion. DESIGN:Case-control study: the OT response to insulin-induced hypoglycaemia was measured in normal and diabetic patients with or without residual endogenous insulin secretion. SUBJECTS:Ten normal male subjects, 10 C-peptide positive (CpP) and 11 C-peptide negative (CpN) male diabetic patients. TESTS: PRELIMINARY STUDIES:plasma C-peptide levels were measured after intravenous administration of 1 mg glucagon. Insulin tolerance test (ITT): diabetics were studied after optimization of their metabolic status by 3 days of treatment with constant subcutaneous insulin infusion. CpP and CpN diabetics and normal controls were tested with an intravenous administration of 0.15 IU per kg body weight insulin. Blood samples for OT assay were taken just before the rapid injection of insulin (time 0) and at time 15, 30, 45 and 60 min. RESULTS:The basal concentrations of OT were similar in all groups. Insulin induced a similar hypoglycaemic nadir in all groups at 30 min, even though diabetic groups showed a delayed recovery in blood glucose levels. The glycaemic pattern was similar in all diabetic patients. Hypoglycaemia-induced OT rise was significantly higher in the two diabetic groups than in the normal group. However, CpN patients showed significantly higher OT increments than CpP subjects. CONCLUSIONS:These data indicate that a residual endogenous insulin secretion exerts a partial protective action against the hypothalamic-pituitary disorder affecting the OT secretory system in IDDM.

To compare both suppressor response and baroreflex sensitivityin disbatic patients (pfs) 3 sympathomimetic agents were injeeted intravenouslyat increasingdoses: norepinephrine (NE), isoprenaline (ISO) and phenylephnne(PHEN).Additionallynitrotrinitrate (Nl) was given sublinguallyduring orthostasjs.27normal persons (NP) and 36 pts were studiad: 15 diabetic pts with nephropathy, 15 hamodialyzednon-diabetic@s, and 6 pts aftar kidney/pancreaatransplantation (Tx), In all persons blood pressure response (AMAP), heart period (AHP), and baroreflexsensitivity(AHPIAMAP) were analyzed.NE end PHEN increased MAP in all diebetic pts (including Tx), ISO (via beta adrenergicreceptors)diminishedMAP in diabetic pts more pronouncedthan in NP or in nondialyzedpts.HP as indicatorof parasympatheticfunction increased in NP efter injeefionof NE or PHEN, while in diabeticpts this responsewaa abolished;in non-diabetic pts it was impaired.After ISO the HP decreased in NP, in diabeticand non-diabeticpts HP was hardiy changed.NI induceda pronounceddecrease of MAP in diabetic pts.The baroreflexsensitivitywas weakenad in all groups.In conclusion, used agents unmasked disturbances of autonomic nervous system In diabetic pts and in nondiabetic pts, respectively.The 132-adrenergic supersensitivity is less distinctthan supersensitivity to rxladrenergicstimulation.

OBJECTIVE:To evaluate the antihypertensive effect of nifedipine gastrointestinal therapeutic system and retard in terms of trough:peak ratio efficacy.METHODS:According to a double-blind, randomized, crossover design, 58 patients with mild-to-moderate essential hypertension, after 1 month placebo washout, received 30 mg/day nifedipine gastrointestinal therapeutic system, 20 mg nifedipine retard twice a day and the corresponding placebos for 1 month. At the end of each treatment period, blood pressure was measured by using a mercury sphygmomanometer at trough and 1, 2, 3 and 4 h after the last dosing. The peak effect was identified as the maximum decrement induced by the three randomized treatments with respect to the value at the end of the placebo washout period during the 4 h interval. The trough:peak ratios of systolic and diastolic blood pressure were calculated as group ratios and individual ratios from decrements induced by nifedipine gastrointestinal therapeutic system and retard, corrected for those induced by randomized placebo. Patients were defined as responders to each randomized treatment if their diastolic blood pressure at trough time was reduced by at least 10 mmHg relative to that at the corresponding time at the end of placebo washout.RESULTS:Nifedipine gastrointestinal therapeutic system and retard significantly reduced blood pressure to a similar extent both at trough and at peak. Systolic and diastolic group trough:peak ratios in responders to nifedipine gastrointestinal therapeutic system (n = 41) were 0.80 and 0.88, respectively, and those in responders to nifedipine retard (n = 30) 0.84 and 0.93, respectively. The percentage of patients with trough:peak ratios > 0.50 was > 80% (systolic trough:peak ratios) and above 90% (diastolic trough: peak ratios) for both nifedipine formulations.CONCLUSIONS:Our data show that 30 mg/day nifedipine gastrointestinal therapeutic system and 20 mg nifedipine retard twice a day have a favourable trough:peak ratios efficacy when given as monotherapy to essential hypertensive patients.

The effect of an i.v. infusion of somatostatin (SRIH) (4.1 micrograms/min/180 min) on angiotensin II (ANG II infusion for 60 min of successively increasing doses of 4, 8 and 16 ng/kg/min; each dose for 20 min)-stimulated growth hormone (GH) and corticotropin (ACTH) release was studied in 7 normal men. In addition, 7 additional normal subjects were tested with ANG II alone (as described above), GH-RH (0.1 microgram/kg body weight as an i.v. bolus) alone or the combination of GH-RH and ANG II. The ACTH response to ANG II was not modified by SRIH infusion; in contrast, the GH response to ANG II was significantly reduced by the concomitant treatment with SRIH. On the other hand, the administration of GH-RH together with ANG II produced peak GH levels comparable to the sum of the individual responses to ANG II and GH-RH, given alone. These findings provide evidence that the stimulatory effect of ANG II on GH, but not ACTH secretion, is under the inhibitory control of somatostatin, suggesting an interaction between ANG II and SRIH in regulation of GH secretion.

To test the possible effects of intravenous administration of substance P (SP) on basal and thyrotropin-releasing hormone (TRH)-stimulated thyrotropin (TSH) release, SP was infused alone (0.5 or 1.5 pmol/kg-1/min-1 for 60 minutes) or after TRH (20 or 400 micrograms in an intravenous bolus) in 21 normal male subjects (aged 26 to 36 years) and in 18 normal women (aged 25 to 32 years). Women were studied during follicular (day 6 to 8) and luteal (day 21 to 23) phases of following regular menstrual cycles. In addition, plasma cortisol levels during SP infusion were measured. In agreement with previous findings, significant increments in plasma cortisol levels were observed in men and women when the higher (1.5 pmol/kg-1/min-1) but not the lower (0.5 pmol/kg-1/min-1) amount of SP was administered. In contrast, in both men and women basal and TRH (20 or 400 mg)-induced TSH releases were not modified by SP at any tested amount. Results in the follicular and luteal phase were similar. These data suggest that in normal men and women plasma SP is not involved in the control of TSH release, at least not outside the blood-brain barrier.

Abstract. Arginine vasopressin (AVP) hypersecretion in response to metoclopramide or to insulin‐induced hypoglycaemia has been described in type I diabetes mellitus. In the present study, we examined whether residual endogenous insulin secretion may play a role in the control of this abnormal AVP secretory pattern. For this purpose, 21 insulin‐dependent diabetic men and 10 age‐ and weight‐matched normal men were tested with MCP (20 mg in an i.v. bolus). On a different occasion, subjects were tested with insulin (0.15IU kg‐1). The diabetic patients were subdivided into C‐peptide negative patients (CpN, 11 patients without detectable endogenous pancreatic β cell activity) (group I) and C‐peptide positive patients (CpP, 10 patients with residual endogenous insulin secretion) (group II). Experiments started after optimization of the metabolic status of the diabetic men by 3 days of treatment with continuous subcutaneous insulin infusion. The basal concentrations of AVP were similar in all groups. The administration of MCP induced a striking elevation in plasma AVP levels in the normal controls and in the diabetic subjects of groups I and II. However, the AVP rise was significantly higher in group I and group II than in normal controls. Furthermore, group I diabetics showed higher AVP increments than group II. Insulin induced a similar hypoglycaemic nadir in all subjects at 30 min, even though the diabetic subjects of groups I and II had a delayed recovery in blood glucose levels. The hypoglycaemic pattern was similar in group I and II. Hypoglycaemia induced a striking AVP increase in the normal controls. However, significantly higher AVP responses to hypoglycaemia were observed in the diabetic men of group I and group II than in the normal controls. Furthermore, group I diabetics showed higher AVP increments than group II. These data indicate that the hypothalamic‐pituitary disorder affecting the AVP response to MCP and insulin‐induced hypoglycaemia in well controlled type I diabetic men is inversely related to residual β‐cell activity.

The effect of oxytocin (OT) on the ACTH response to the intravenous administration of Endothelin-1 (ET-1) was investigated in 7 normal men. ET-1 was given alone at a dose of 5.0 ng/kg/min for 15 min plus 2.5 ng/kg/min for 105 min or together with OT (2 I:U. injected plus 4 I.U, infused over 2 hours). In addition, control tests with normal saline instead of drugs were performed. No significant change in ACTH secretion was observed during the control test. In contrast, within 20 min ET-1 induced a significant increase in serum ACTH levels which continued with a plateau during infusion. The concomitant administration of OT significantly reduced the ACTH response to ET-1 infusion. During ET-1 and OT combined treatments, ACTH values were slightly higher, but not significantly different from those observed in the control test. These data confirm the stimulating effect of ET-1 on ACTH secretion in normal men; furthermore, our results show that ET-1-induced ACTH rise is sensitive to OT inhibition, suggesting a possible interaction between ET-1 and OT in the control of ACTH secretion.

In order to establish whether endogenous opioids modulate the LH response to systemically-infused Substance P (SP), seven normal men (24-33 yr) were infused with SP (0.5 or 1.5 pmol/kg(-1)/min(-1) for 60 min), naloxone (0.0.2 mu g/kg(-1)/min(-1) for 60 min) or the combination of SP and naloxone. The lower dose of SP (0.5 pmol/kg(-1)/min(-1)) was unable to change the plasma levels of LH. The infusion of naloxone induced a slight, but significant increase in plasma LH concentrations (34% increase vs baseline). A similar response was found when naloxone was given together with the lower dose of SP. A striking increase in plasma LH was observed during the infusion of the higher dose of SP (1.5 pmol/kg(-1)/min(-1)) (93% vs baseline). A slightly higher LH increase (111% vs baseline) was observed when naloxone plus the higher dose of SP was infused. However, the LH increment was not significantly different from that observed during the infusion of SP (1.5 pmol/kg(-1)/min(-1)) alone.These data confirm the stimulating effect of systemically-infused SP on LH release, without evidence of the involvement of naloxone-sensitive endogenous opioids in the mechanism of action of SP.

The possible involvement of endogenous opioids in the gamma-aminobutyric acid-controlled (GABAergic) inhibition of growth hormone (GH) and prolactin (PRL) during physical exercise was evaluated in normal men. After fasting overnight, seven subjects were tested on four mornings at least 1 week apart. Exercise was performed on a bicycle ergometer. The workload was gradually increased at 3-min intervals until exhaustion and lasted about 15 min in all subjects. Tests were carried out under administration of placebo, the opioid antagonist naloxone (10 mg as an iv bolus injection), the GABAergic agonist sodium valproate (600 mg in three divided doses orally) or naloxone plus sodium valproate. During exercise, plasma GH and PRL levels rose 5.5- and 1.9-fold, respectively. The administration of naloxone did not modify, whereas sodium valproate significantly reduced the plasma GH and PRL rise during exercise. In the presence of sodium valproate, GH and PRL levels rose 3- and 1.5-fold, respectively, in response to exercise. When naloxone was given together with sodium valproate, both GH and PRL responses to exercise were abolished completely. These data suggest the involvement of a GABAergic mechanism in the regulation of GH and PRL responses to physical exercise in men. Furthermore, the data argue against a role of naloxone-sensitive endogenous opioids in the control of these hormonal responses to exercise, whereas they suggest a modulation by opioids of the GABAergic inhibitory action.

The present study was carried out in order to establish possible alterations in oxytocin (OT) secretion with aging. Therefore, we evaluated the OT responses to insulin (0.15 U/kg)-induced hypoglycemia or to the administration of angiotensin II (i.v. infusion for 60 min of successively increasing doses of 4, 8 and 16 ng/kg min; each dose for 20 min) or apomorphine (60 micrograms/kg s.c.) in male subjects aged 22-80 yr and divided into 3 groups by age (group I (n = 9): 22-38 yr; group II (n = 9): 41-60 yr; group III (n = 9): 63-80 yr). Basal OT concentrations were similar in all groups. The OT response during the insulin tolerance test and the administration of ANG II had similar patterns and magnitudes in all groups. The OT response to apomorphine was similar in the two younger groups, with plasma OT levels increased 118% vs. baseline. In contrast, apomorphine was unable to induce a significant OT rise in the oldest group. During apomorphine test plasma OT concentrations were significantly lower in group III than in groups I and II. For the first time in elderly human subjects, these data show normal responsiveness of the OT secretory system to releasing stimuli such as hypoglycemia and ANG II. These findings indicate that in aged men production of OT and capability of responding to challenging stimuli is unchanged. On the other hand, the reduced OT responsiveness to apomorphine in group III might be an expression of the general dopaminergic dysfunction affecting the aging brain.