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 μg·kg −1·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 μg·kg −1·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 μg·kg −1·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.