CGP 22979A, a Renal Vasodilator with Natriuretic Properties

Renal vasodilation might be an interesting new antihypertensive principle. In the present study, the prodrug approach was adopted to synthesize a preferential renal vasodilator. A hydralazine-like compound, CGP 18137A (2-hydrazino-5-n-butyl-pyridine), was substituted with an N-acetyl-gamma-glutamyl residue. The resulting derivative, CGP 22979A [N-acetyl-L-glutamic acid-N[N2-(5-n-butyl-2-pyridyl)hydrazide]], was inactive in the isolated perfused mesenteric artery, whereas the parent compound induced a dose-dependent inhibition of vasoconstrictor stimuli. When administered i.v. to anesthetized rats in doses between 1.0 and 10.0 mg/kg, CGP 22979A increased renal blood flow significantly, by up to 31% without affecting blood pressure. A dose of 4.0 mg/kg lowered renal vascular resistance by 25% but did not alter total systemic, mesenteric and iliac vascular resistance. A dose of 10.0 mg/kg increased glomerular filtration rate by up to 42%. In conscious rats, the same dose increased sodium excretion by 200%. Because CGP 22979A induces renal vasodilation in rats and has a preferential action on the afferent arterioles, it might be a useful tool for studying the antihypertensive potential of renal vasodilation.