AJP - Renal Physiology, Vol 259, Issue 2 304-F311, Copyright © 1990 by American Physiological Society
Efficacy of nifedipine to prevent systemic and renal vasoconstrictor effects of endothelin
P. Madeddu, X. P. Yang, V. Anania, C. Troffa, A. Pazzola, A. Soro, P. Manunta, G. Tonolo, M. P. Demontis, M. V. Varoni and al. et
Clinica Medica and Farmacologia, University of Sassari, Italy.
We investigated whether systemic and renal vasoconstriction induced by
porcine endothelin (endothelin 1) is prevented by nifedipine in awake
normotensive rats. Endothelin (0.07-1.4 nmol/kg iv) induced a long-lasting
increase in mean blood pressure (MBP) and a decrease in renal blood flow
(RBF). Maximal decrease in RBF was 25 +/- 7% (0.07 nmol/kg), 40 +/- 2
(0.35), 67 +/- 5 (0.70), and 74 +/- 8 (1.4). Hemodynamic parameters were
back to base line within 35 +/- 5 min (0.07 nmol/kg), 43 +/- 6 (0.35), 60
+/- 4 (0.70), and 81 +/- 7 (1.4). Intravenous bolus injection of either
angiotensin II (ANG II, 0.006-0.024 nmol/kg) or norepinephrine (0.40-1.60
nmol/kg) caused a dose-related short-lasting increase in MBP and a decrease
in RBF. Endothelin was less potent than ANG II (1:3.42) and more potent
than norepinephrine (1:0.015) as a renal vasoconstrictor. Nifedipine (1
mg/kg ip) was equally effective in preventing the increase in MBP caused by
endothelin, norepinephrine, or ANG II. It exerted a weaker protection on
the renal hemodynamic response to endothelin compared with the inhibition
of the other two vasoconstrictors. Thus the regression line representing
the relationship between endothelin-induced changes in MBP and RBF was
steeper in rats given nifedipine (slope: vehicle, -1.33; nifedipine, -5.50;
P less than 0.05). These studies suggest that nifedipine can partially
prevent systemic and renal vasoconstriction caused by exogenously
administered endothelin in awake normotensive rats.
