SUMMARY Adrenal and vascular responsiveness to graded doses of angiotensin II (A II) were recorded for seven normal subjects and 12 patients with essential hypertension while in balance on an intake of 200 mEq sodium/100 mEq potassium. Patients with essential hypertension had been previously studied and known to have normal responses of plasma renin activity to sodium restriction and upright posture. A l l was administered for 30 minutes at rates of 0.1, 0.3, 1, and 3 ng/kg per minute and plasma aldosterone responses were assessed 20 and 30 minutes later; blood pressure was monitored at intervals of 1 minute during infusion of A 11 at each rate. A significant increment in plasma aldosterone occurred at an infusion rate of 0.3 ng/kg per minute in patients with hypertension. This change was not seen until the infusion rate reached 1.0 ng/kg per minute in the normotensive control subjects. Even at an A II infusion rate of 1 ng/kg per minute, the increment in plasma aldosterone levels in normotensive subjects (4.2 ± 0.6 ng/dl) was significantly less (P < 0.001) than that in patients with essential hypertension (19 ± 3 ng/dl). In both groups, a significant rise in mean arterial blood pressure occurred at an A II dose of 0.3 ng/kg per minute, but the pressor response of the hypertensive group was significantly greater at the highest infusion rate (3 ng/kg per minute) (P < 0.05). Thus, enhanced adrenal and pressor responsiveness to infused A II was observed in the hypertensive subjects, suggesting a change in A II receptor affinity.ANGIOTENSIN II may play an important role in the control of blood pressure through its vasoconstrictor activity as well as its effects on volume homeostasis exerted through regulation of aldosterone secretion. However, previous studies evaluating adrenal and vascular responsiveness to infused angiotensin II (A II) in hypertensive subjects have yielded conflicting results.1 ' 6 Moreover, recent studies suggest that there may be physiologically important but functionally different receptors for A II on the adrenal cortex and vascular smooth muscle.7 ' 9 An imbalance of the relative responsivenes of these receptors to A II might lead to an imbalance in volume homeostasis or vasoconstrictor activity and thus produce an elevated blood pressure. The present study was designed to compare the relative magnitude of response of blood pressure and aldosterone secretion to graded doses of A II in patients with essential hypertension and normal subjects. MethodsTwelve patients with essential hypertension and seven normotensive control subjects were studied in the Clinical Research Center of the Peter Bent Brigham Hospital. The normotensive subjects (five male, two female) ranged in age from 23 to 38 years. They denied use of drugs and had no evidence of renal, cardiovascular, or endocrine abnormalities on routine screening. Patients with essential hypertension (eight male, four female) ranged in age from 24 to 68 years. The criteria for inclusion of patients with hyperten- sion in the study were as follo...

Hypertension is often cited as a risk factor for erectile dysfunction. To clarify the relation between hypertension and erectile dysfunction, we evaluated 32 consecutive hypertensive and 78 normotensive impotent men with respect to multiple potential determinants and parameters of erectile function, including medical and sexual history, depression, hormonal profile, penile nocturnal tumescence, penile vascular supply, and pudendal nerve conduction. The hypertensive men were older, had higher body mass index, and used more medications than the normotensive men. The groups were not different with respect to the prevalence of smoking and peripheral vascular disease, but the hypertensive men had a marginally higher rate of ischemic heart disease (P = .06). The prevalence of depression, abnormal nocturnal penile tumescence, anomalous pudendal nerve conduction, and impairment in arterial supply as determined by penile brachial index were similar in the two groups. Testosterone and bioavailable testosterone levels were lower in the hypertensive men. After stratification by age and body mass index, hypertensive men younger than 50 years with body mass index less than 30 kg/m2 had significantly lower testosterone levels (12.0 +/- 1.7 versus 21.3 +/- 1.4 nmol/L, P < .02) but not bioavailable testosterone levels (3.9 +/- 0.7 versus 6.4 +/- 0.7 nmol/L, P < .17) than the corresponding normotensive group. Prolactin, follicle-stimulating hormone, and luteinizing hormone levels of the two groups were not significantly different. Contrary to common belief and with the exception of lower circulating testosterone levels, the overall analysis showed little difference between hypertensive and normotensive men with respect to a wide range of classic determinants of erectile function. Direct study of the local vascular erectile apparatus appears necessary for further elucidation of the mechanisms underlying erectile dysfunction in hypertensive men.

The 24-hour pattern of plasma cortisol concentration in four patients on the day before major elective surgery was compared with that of five similarly hospitalized control subjects to study the effect of the expectation of surgery on the secretion pattern. Using an indwelling venous catheter, which extended outside the patient's room, to collect blood samples every 20 minutes for 24 hours, it was found that cortisol was secreted episodically in both control subjects and presurgical patients. The nychthermal patterns of plasma cortisol concentration in the two groups were indistinguishable for most of the day despite the occurrence of intermittent events which appeared to cause anxiety in the presurgical patients. However, between 9 PM and 11 PM, while each presurgical patient was being preoperatively prepared (body shaving, wash, and enema), a major pulse of cortisol secretion occurred, raising the plasma cortisol concentration to between 6.9-10.5 standard deviations above that of the control subject mean for that time of day. We conclude that 1) expectation of a major surgical procedure for several weeks does not result in chronic activation of the pituitary-adrenocortical axis, 2) many discrete anxiety-provoking events do not evoke cortisol secretory episodes, 3) most episodes of cortisol secretion are part of an endogenous cyclical pattern with a circadian distribution and are not a direct result of environmental stimuli, and 4) preoperative preparation evokes a major cortisol secretory response in patients awaiting surgery. Whether that release of cortisol is a response to the physical manipulations or the psychological implications of that stimulus is presently unknown.

We have previously reported that the nonselective lipoxygenase inhibitor phenidone is a potent hypotensive agent in the spontaneously hypertensive rat (SHR). In the present study, we examined the relationship between production of platelet 12-hydroxyeicosatetraenoic acid (12-HETE) and intra-arterial blood pressure in SHR and Wistar-Kyoto rats (WKY) using both a cross-sectional analysis and an acute pharmacological intervention. Basal generation rate of 12-HETE by platelets collected from the SHR was approximately 3.7-fold higher than in the WKY (0.86 +/- 0.24 versus 0.23 +/- 0.05 nmol/mL per 10 minutes, respectively; P < .01). Systolic arterial pressure was positively related to platelet 12-HETE formation rate when the entire rat population was considered (r = .70, P < .001). The specific 12-lipoxygenase inhibitor cinnamyl-3,4-dihydroxycyanocinnamate induced lowering of both arterial blood pressure and platelet 12-lipoxygenase activity in SHR. At 15 mg/kg, cinnamyl-3,4-dihydroxycyanocinnamate elicited a marked hypotensive effect in SHR but not in WKY. This reduction in arterial pressure was accompanied by an approximate 70% inhibition in platelet 12-HETE production rate. The return of high blood pressure to basal levels was associated with a significant rise in the production of platelet 12-HETE toward control values (baseline, 0.97 +/- 0.33 nmol/mL per 10 minutes; nadir of blood pressure, 0.19 +/- 0.03; resumption of basal pressure, 0.42 +/- 0.14). In contrast, captopril (15 mg/kg) induced a quantitatively similar decrease in blood pressure but had no effect on platelet 12-HETE generation rate. Thus, hypertension in SHR is linked to increased production rate of platelet 12-HETE. Acute blood pressure reduction attained during lipoxygenase inhibition but not by angiotensin converting enzyme inhibition leads to a concomitant reduction in the production of platelet 12-HETE. We speculate that since rat arterial tissue produces 12-HETE, increased 12-lipoxygenase activity in SHR may contribute to the maintenance of elevated arterial pressure in this strain.