Effects of nifedipine treatment on the renin-angiotensin-aldosterone axis.
Nifedipine is a commonly used agent in treating hypertension and angina because of its vasodilator properties. An inhibitory role of nifedipine on aldosterone (Aldo) biosynthesis has been documented in in vitro studies. This study was designed to examine the impact of a sustained release nifedipine formulation on Aldo biosynthesis and its clinical consequences. Early and late effects of nifedipine on Aldo, PRA, and Aldo/PRA ratio levels were studied in a single blind, placebo-controlled, 10-day pilot study. Ten normotensive subjects and 10 patients with hypertension were studied. Blood samples for the measurement of Aldo and PRA were obtained at 2-h intervals for 10 h on a control day and on days 1 and 8 of nifedipine treatment for the determination of baseline, early, and late values. Placebo was administered at 0800 h on the first and second days of the study, whereas nifedipine (60 mg/day) was given for the following 8 days. The Aldo/ PRA ratio was used as a sensitive indirect index of the responsiveness of Aldo secretion to adrenal stimulation with angiotensin. Compared to those on the control day, a significant rise in the integrated PRA levels occurred on the first day of nifedipine treatment, with a further rise observed on the eighth day of the treatment in the normotensive subjects (1.1 +/- 0.6, 1.7 +/- 1.2, and 2.5 +/- 1.8 ng/mL.h on the control day and the first and eighth days of treatment, respectively; P < 0.05) and by the eighth day in the hypertensive subjects (2.2 +/- 2.8 and 4.0 +/- 4.1 ng/mL.h; P < 0.05). A significant rise in integrated Aldo levels occurred in the normotensive subjects on the eighth day of nifedipine treatment (control day, 319 +/- 187; eighth day of nifedipine, 363 +/- 167 pmol/L; P < 0.05) and in the hypertensive subjects (426 +/- 219 and 535 +/- 284 pmol/L; P < 0.05). This was associated with a significant lowering of the Aldo/PRA ratio on the first day of the treatment, with further lowering on the eighth day in the normotensive (435 +/- 454, 269 +/- 209, and 182 +/- 107; P < 0.05) and by the eighth day in the hypertensive subjects (716 +/- 833 and 305 +/- 315; P < 0.05). When individual time points were examined in the normotensive subjects, Aldo/PRA levels were significantly lower on day 8 of nifedipine treatment at 1000, 1200, and 1400 h than corresponding values on the control day. The fall in the Aldo/PRA ratio during nifedipine treatment indicates that the previously reported in vitro inhibition of Aldo biosynthesis in adrenal cells is reproduced in vivo. In the absence of nifedipine, it is likely that Aldo levels would be higher for any given level of PRA. It is probable that the Aldo inhibition and the vasodilatatory effect of nifedipine combine to bring about the lowering of blood pressure. Drugs that inhibit renin-angiotensin axis activity are likely to be particularly effective when additional lowering of blood pressure is required.
Fiad
T M
TM
Department of Investigative Endocrinology, University College Dublin, Ireland.
Cunningham
S K
SK
Hayes
F J
FJ
McKenna
T J
TJ
D000368:Aged; D000450:Aldosterone / Q000097:blood / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000008:administration & dosage / Q000627:therapeutic use*; D012016:Reference Values; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013997:Time Factors; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*
D003692:Delayed-Action Preparations; D014665:Vasodilator Agents; D000450:Aldosterone; D012083:Renin; D009543:Nifedipine