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Abstract
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.
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© 1983 Published by Elsevier Inc.