Antihypertensive and haemodynamic properties of the renal vasodilator CGP 22 979A in conscious spontaneously hypertensive rats.

The acute haemodynamic and long-term antihypertensive properties of the renal vasodilator pro-drug CGP 22 979A (N-acetyl-L-glutamic acid-N-[N2-(5-n-butyl-2- pyridyl)-hydrazide]) were studied in conscious, chronically instrumented spontaneously hypertensive rats (SHR). Its effects were compared with those of its parent substance CGP 18 137A (2-hydrazino-5-n-butyl-pyridine) which is a general arteriolar dilator. CGP 18 137A (0.3-1 mg/kg) caused an immediate reduction in mean arterial pressure (MAP) and total peripheral resistance index (TPRI). These effects were paralleled by reflex increases in heart rate (HR) and cardiac index (CI). In high doses CGP 22 979A (30 mg/kg) caused similar effects. In contrast, lower doses of CGP 22 979A (3-10 mg/kg) did not reduce MAP or TPRI acutely. However, these doses caused a more gradual reduction in MAP without reflex increase in HR or CI. In long-term experiments a 7-day continuous infusion of CGP 18 137A (0.1-1 mg/kg per day) or a high rate of CGP 22 979A (30 mg/kg per day) reduced MAP with parallel reflex rises in HR. Ten mg/kg per day CGP 22 979A caused a gradual reduction in MAP without reflex tachycardia.