Antihypertensive contribution of sodium depletion and the sympathetic axis during chronic angiotensin II converting enzyme inhibition.
The known physiological adaptation of cardiovascular sensitivity to variations in angiotensin II (Ang II) levels would predict that the blood pressure (BP)-lowering effect of Ang II inhibition might be at least partly counterbalanced by enhanced Ang II reactivity. Therefore, factors other than Ang II inhibition per se may contribute to the antihypertensive mechanisms of angiotensin converting enzyme (ACE) inhibitors. In order to further investigate this, the body sodium-blood volume state as well as the pressor reactivity to infused Ang II or norepinephrine (NE) were assessed in 12 normal subjects and 16 patients with essential hypertension given a placebo, and after 6 weeks of intervention with enalapril (20-40 mg/day). Enalapril produced in both groups similar falls in plasma ACE activity (P less than 0.0001) and upright plasma aldosterone (P less than 0.01), and a rise in plasma renin activity (PRA; P less than 0.05). BP decreased from 156/107 +/- 3/2 (mean +/- s.e.m.) to 142/94 +/- 5/3 mmHg (P less than 0.001) in the hypertensives and from 118/84 +/- 4/2 to 111/73 +/- 4/3 mmHg (P less than 0.01) in the normal subjects. In the hypertensive patients only, the Ang II pressor reactivity relative to Ang II plasma levels during Ang II infusion was increased (P less than 0.01), while the NE pressor reactivity relative to NE plasma levels during NE infusion (P less than 0.01) as well as the exchangeable body sodium (-5%, P less than 0.001) were reduced significantly. Blood and plasma volume, levels of plasma atrial natriuretic factor and catecholamines, and the heart rate and its response to isoproterenol were unchanged in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Uehlinger
D E
DE
Medizinische Poliklinik, University of Bern, Switzerland.
Ferrier
C P
CP
Matthieu
R
R
Reuter
K
K
Gnaedinger
M P
MP
Saxenhofer
H
H
Shaw
S
S
Weidmann
P
P
D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000008:administration & dosage / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena; D004039:Diet, Sodium-Restricted; D004656:Enalapril / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D007545:Isoproterenol / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000008:administration & dosage / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D011897:Random Allocation; D016037:Single-Blind Method; D012964:Sodium / Q000378:metabolism; D013997:Time Factors
D000804:Angiotensin II; D004656:Enalapril; D012964:Sodium; D007703:Peptidyl-Dipeptidase A; D007545:Isoproterenol; D009638:Norepinephrine