Effects of Nadolol, a new beta-adrenoceptor blocking agent, on blood pressure and renal function in experimental hypertensive animals.

Abstract

Nadolol, 2,3-cis-1,2,3,4-tetrahydro-5-{2-hydroxy-3-(tert-butylamino) propoxy}-2,3-naphthalenediol, is a non-selective β-adrenergic blocking agent without intrinsic sympathomimetic and membrane stabilizing activity. The effects of Nadolol on blood pressure and renal function in renal hypertensive dogs(RHDogs, two-kidney two-clip, at 2-3 months after the clipping) and spontaneously hypertensive rats(SHR) were compared with those of other β-blocking agents(Propranolol, Alprenolol and Pindolol). 1) In RHDogs, Nadolol(3 or 10mg/kg/day p.o. for 10 days) showed a long lasting antihypertensive effect and β-blocking activity. Nadolol did not decrease the renal blood flow(RBF), glomerular filtration rate(GFR), urine flow(UF) and urinary Na+ and K+ excretion. However, Alprenolol(20mg/kg/day) and Pindolol (1 or 3mg/kg/day) decreased significantly the RBF and urinary Na+ excretion at 5 hour after administration. 2) In SHR(16 weeks old), Nadolol did not show an antihypertensive activity as with other β-blocking agents. On the other hand, in the SHR provided a low-sodium diet(Na 0.0014%), Nadolol(30 mg/kg p.o.) decreased significantly the blood pressure after single or repeated administration for 4-7 days, the same as other β- blocking agents. 3) With immature SHR(4 weeks old), chronic oral administration of Nadolol (3 or 10mg/kg/day for 8 weeks) suppressed the development of hypertension, but did not influence urinary Na+ and K+ excretion. These results indicated that Nadolol appeared to be a long lasting antihypertensive drug without adverse effects on renal function, and Na-depleted SHR was a suitable model for the evaluation of antihypertensive activity of β-blocking agents.