K. Schricker et al., ROLE OF ENDOGENOUS ENDOTHELINS IN THE RENIN SYSTEM OF NORMAL AND 2-KIDNEY, ONE-CLIP RATS, Hypertension, 25(5), 1995, pp. 1025-1029
This study aimed to investigate the relevance of endogenous endothelin
s in the control of renin secretion and renin gene expression under ba
sal conditions and stimulated conditions achieved with unilateral rena
l artery stenosis. To this end, we studied the effects of the orally a
ctive endothelin antagonist Ro 47-0203 (100 mg/kg per day) for 2 days
on plasma renin activity and renal renin mRNA levels in normal rats an
d rats with unilateral renal artery clips (0.2 mm). Treatment with Ro
47-0203 did not change basal arterial pressure but significantly atten
uated the rise of blood pressure in response to renal artery clipping.
Although Ro 47-0203 tended to increase basal plasma renin activity, t
his effect was not significant. Basal renin mRNA levels of kidneys wer
e also not changed by the drug. Unilateral renal artery clipping incre
ased plasma renin activity from 12 to 34 ng angiotensin I/mL per hour,
increased renin mRNA levels to 328% of controls in the clipped kidney
s, and decreased renin mRNA levels to 23% of controls in the contralat
eral intact kidneys. These changes were not influenced by Ro 47-0203.
In isolated perfused rat kidneys, Ro 47-0203 (10 mu mol/L) also had no
effect on basal renin secretion or vascular resistance, but it substa
ntially attenuated the decrease of renin secretion and renal flow in r
esponse to administration of exogenous endothelin. Taken together, the
se findings suggest that endogenous endothelins play no relevant role
in the control of renin secretion and of renin gene expression in norm
al and hypoperfused rat kidneys.