Vascular pressor responses in treated and untreated essential hypertension.
Thirty-seven essential hypertensives received placebo for 3 weeks followed by nifedipine retard (n = 14) or enalapril (n = 13) or doxazosin (n = 10) as monotherapy for 6 weeks and attended study days to evaluate the effects of placebo, first dose, and chronic (1-6 weeks) treatment. On each study day, pressor responses to i.v. infusions of phenylephrine (PE) and angiotensin II (AII) were measured 1.5-3 h after drug administration and the derived PD20 values (dose required to increase mean blood pressure by 20 mm Hg) compared. Each treatment produced comparable reductions in BP. Nifedipine significantly attenuated the pressor responses to AII and PE: for AII, the mean PD20 (ng/kg/min) increased from 8.2 (placebo) to 9.9 (first dose), 13.9 (1 week), and 17.4 (6 weeks). Pressor responsiveness to both AII and PE was unchanged following enalapril: for PE, the mean PD20 (micrograms/kg/min) was 2.1 (placebo), 1.5 (first dose), and 1.5 (6 weeks). Doxazosin produced rightward shifts of the PE pressor dose-response curves but had no effect on responses to AII. The relationship between the simultaneous BP and HR changes during the infusion of PE was used as an index of cardiac baroreflex activity. In contrast to enalapril and doxazosin, which had no effect, nifedipine reduced the slope of the HR/BP relationship from -0.62 (placebo) to -0.38 (first dose) and -0.31 beats/min/mm Hg (6 weeks). For comparable reductions in BP, doxazosin only affects adrenergic mechanisms whereas nifedipine affects both adrenergic and non-adrenergically mediated vasoconstriction. The ACE inhibitor enalapril had no effect on pressor responses to AII and PE.
University Department of Medicine and Therapeutics, Stobhill General Hospital, Glasgow, Scotland.
R
R
Donnelly
H L
HL
Elliott
C A
CA
Howie
D J
DJ
Sumner
J L
JL
Reid
D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000097:blood; D017292:Doxazosin; D004656:Enalapril / Q000097:blood / Q000627:therapeutic use; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000097:blood / Q000627:therapeutic use; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D010656:Phenylephrine / Q000097:blood / Q000627:therapeutic use; D011224:Prazosin / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use; D012018:Reflex / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D012083:Renin / Q000097:blood
D000959:Antihypertensive Agents; D002395:Catecholamines; D000804:Angiotensin II; D010656:Phenylephrine; D000450:Aldosterone; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D009543:Nifedipine; D017292:Doxazosin; D011224:Prazosin