Cicletanine modulates endothelin-induced renal vasoconstriction in the rat.
Endothelin (ET-1), a recently discovered endothelium-derived peptide, has been reported to produce potent vasoconstriction in various isolated vessels of experimental animals. Cicletanine (CIC) is a novel antihypertensive agent. This study concerns the effect of CIC on the vascular actions of ET-1 (0.2 nM/kg) and epinephrine (1 microgram/kg) in normotensive Wistar rats. The hemodynamic effects of ET-1 and epinephrine were also tested in the presence of molsidomine (MOL), a vasodilator that releases nitric oxide. Rats were treated for 15 days with CIC (10 mg/kg/day) or gum arabic p.o. Subsequently, the animals were anesthetized and renal and aortic blood flow (BF) determined by pulsed Doppler flowmetry. ET-1 or epinephrine was injected. After return to the basal level, MOL (5 mg/kg) was injected; 10 min later, the mean arterial pressure (MAP) was decreased and then ET-1 or epinephrine was administered. The vascular resistance was calculated by the MAP/BF ratio and expressed as a percentage. In CIC-treated rats, ET-1 induced a renal vasoconstriction smaller than in control rats (+27.2 +/- 5.95 and +60.4 +/- 11.95%, respectively, p less than 0.01). In the presence of MOL, ET-1 produced a smaller increase in MAP (+9.7 +/- 1.34 and +16.9 +/- 2.49 mm Hg, p less than 0.05). Epinephrine injected after MOL in CIC-treated rats induced a smaller renal vasoconstriction than in control rats (+98.8 +/- 29.83 and 185 +/- 30.33%, p less than 0.05). Thus, CIC partially reduced the hypertensive and renal vasoconstrictor effects of ET-1. A combination of CIC and MOL diminished the renal effects of epinephrine. In conclusion, CIC could be used to attenuate the hypertensive status or renal ischemia disorders where ET-1 seems to be implicated.
Cornet
S
S
Institut Henri Beaufour Research Laboratories, Les Ulis, France.
Teillot
M
M
Pirotzky
E
E
Braquet
P
P
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004232:Diuretics / Q000494:pharmacology*; D016232:Endothelins / Q000494:pharmacology*; D004837:Epinephrine / Q000494:pharmacology; D008981:Molsidomine / Q000494:pharmacology; D011725:Pyridines; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction
D000959:Antihypertensive Agents; D004232:Diuretics; D016232:Endothelins; D011725:Pyridines; C038068:cicletanine; D008981:Molsidomine; D004837:Epinephrine