Role of renin release in the hemodynamic, renal and dipsogenic actions of the prostacyclin analogue CG 4203 in conscious rats.
The influence of CG 4203, a chemically and metabolically stable prostacyclin analogue, on plasma renin activity, arterial blood pressure, renal function and water intake was investigated in conscious rats. CG 4203 infused intravenously starting at 1 microgram X kg-1 X min-1 induced both a fall in blood pressure and an increase of plasma renin activity. The angiotensin II antagonist saralasine infused simultaneously intensified the hypotensive effect of CG 4203 (1.0 microgram X kg-1 X min-1). Within a similar dose range CG 4203 dose-dependently inhibited diuresis and saluresis and reduced the urinary sodium/potassium ratio. These effects were partially reversed by adrenalectomy and completely abolished by pretreatment with the angiotensin I converting enzyme inhibitor captopril. Similarly, CG 4203 (0.21 - 4.64 micrograms X kg-1 X min-1) dose-dependently caused increased water intake which was prevented by previous nephrectomy. In conclusion, it is demonstrated that CG 4203 like prostacyclin itself already at hypotensive threshold dosages stimulates a functionally relevant renin release. The activation of the renin-angiotensin-aldosterone system attenuates the intrinsic hypotensive effects of CG 4203. the antidiuretic and dipsogenic efficacy of CG 4203 can also be attributed to renin-dependent angiotensin II formation.
D000315:Adrenalectomy; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D004326:Drinking / Q000187:drug effects*; D011464:Epoprostenol / Q000494:pharmacology* / Q000031:analogs & derivatives; D007668:Kidney / Q000502:physiology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood*; D012504:Saralasin / Q000494:pharmacology
C039188:taprostene; D002216:Captopril; D011464:Epoprostenol; D012083:Renin; D012504:Saralasin