Increase in plasma renin activity evoked by fenoldopam in dogs is directly mediated by dopamine1 receptor stimulation.
In anesthetized dogs, a 15-min intravenous (i.v.) infusion of fenoldopam (2.0 micrograms/kg/min) produced a decrease in mean aortic blood pressure (MAP) and an increase in renal blood flow (RBF) and plasma renin activity (PRA). The hypotensive effect attained a maximum within 5 min and then waned by approximately 30% at the end of fenoldopam administration. The development of this "tolerance" phenomenon was prevented by enalapril or saralasin. The hypotension and the increase in PRA were not modified by either propranolol or chlorisondamine but were inhibited by SCH 23390, a DA1 antagonist. Fenoldopam (0.1 microgram/kg/min for 15 min) infused into the left renal artery (i.a.) in intact or ganglion-blocked dogs did not change MAP but increased PRA. This effect was antagonized by SCH 23390. In ganglion-blocked preparations in which an apparently maximal renal vasodilatation had been achieved by an i.a. acetylcholine, i.a. fenoldopam produced an increase in PRA which was again blocked by SCH 23390. In uninephrectomized dogs, blockade of alpha- and beta-adrenoceptors or inhibition of renal baroreceptor and macula densa mechanisms of renin release failed to prevent the fenoldopam-induced increase in PRA. In conclusion, the release of renin by fenoldopam is responsible for the development of tolerance to the hypotensive effects of fenoldopam. Furthermore, because the increase in PRA was blocked by SCH 23390 and occurred in the absence of either operational systemic or intrarenal regulatory mechanisms, we propose that it is mediated by stimulation of specific dopamine (DA1) receptors on the juxtaglomerular (JG) cells.
Montier
F
F
Rhône-Poulenc Santé, Centre de Recherche de Vitry, Vitry-sur-Seine, France.
Katchadourian
P
P
Pratz
J
J
Cavero
I
I
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002714:Chlorisondamine / Q000494:pharmacology; D004285:Dogs; D004656:Enalapril / Q000494:pharmacology; D005260:Female; D018818:Fenoldopam; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000187:drug effects*; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood*; D013268:Stimulation, Chemical
D001552:Benzazepines; D011954:Receptors, Dopamine; D004656:Enalapril; D011433:Propranolol; D012083:Renin; D018818:Fenoldopam; D002714:Chlorisondamine; D000109:Acetylcholine; D011224:Prazosin; D007213:Indomethacin