The effect of vasopressin released by cigarette smoking on blood pressure (BP), heart rate (HR), and skin blood flow (SBF) was investigated in 12 normotensive habitual smokers. At a 1-wk interval, each subject smoked within 10 min two cigarettes before and after intravenous injection of either the specific vascular vasopressin antagonist d(CH2)5Tyr(Me)AVP (5 micrograms/kg) or its vehicle administered in double-blind fashion. SBF was assessed with a laser Doppler flowmeter. Smoking increased plasma vasopressin (P less than 0.01). In six subjects subsequently treated with the antagonist, plasma vasopressin rose to greater than 10 pg/ml and SBF fell by 18.2 +/- 4.8%. This SBF reduction was prevented by the vasopressin antagonist. In contrast, the vehicle had no effect. In the 24 studies taken together, there was a significant correlation (r = -0.60, P less than 0.01) between the SBF decrease during the first smoking period and the plasma vasopressin levels measured afterwards. The BP and HR rise caused by smoking was not modified by the antagonist. Thus it appears that the decrease in SBF induced by smoking is due to enhanced vasopressin secretion.
The new orally active angiotensin converting enzyme (ACE) inhibitor perindopril (S9490-3) was evaluated in 18 normotensive men. In three subjects the pressor response to exogenous angiotensin I was tested. A 8 mg oral dose reduced the pressor response by greater than 80%. Single oral perindopril doses of 2, 4, 8, and 16 mg were given to groups of five subjects each. Eight and 16 mg decreased plasma ACE activity within 4 hours to less than 10% of control; 72 hours later, plasma ACE activity was still reduced by at least 40%. Doses of 4 and 8 mg po once a day were then given for 8 days to two groups of six subjects. Four hours after the first and the last morning doses, plasma angiotensin II, aldosterone, and plasma ACE activity fell significantly, whereas blood angiotensin I and plasma renin activity rose. There was no evidence of drug accumulation. No significant change in blood pressure or heart rate was observed. Thus in normotensive subjects, perindopril seems an effective, orally active, long-lasting ACE inhibitor.
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