Cardiovascular responses to acute and subchronic treatment with oxprenolol in spontaneously hypertensive rats at rest and at stress.

Abstract

To further examine the mechanism of antihypertensive action, effects of a single (50mg/kg) and repeated oral administration (50 mg/kg per day, for 14 days) of oxprenolol on mean arterial pressure (MAP) and heart rate (HR) were studied in spontaneously hypertensive (SHR) rats at rest and during handling stress. MAP was measured through a indwelling aortic cannula and HR was determined via chronically implanted electrodes. A single oral dose of oxprenolol produced a gradual fall in resting MAP. Although repeated dose of oxprenolol did not alter the developmental course of hypertension in SHR rats, a prompt and significant fall in MAP at rest was observed after the dose on the 14th day of the experiment. A single and repeated dose of oxprenolol attenuated the increase in MAP during handling stress, but these effects were less apparent when compared to the fall in resting MAP. Significant reductions in stress-induced tachycardia were observed both after a single and repeated dose, whereas resting HR tended to increase. These results indicate that some of the postulated antihypertensive mechanisms such as central inhibition of sympathetic outflow, peripheral inhibition of sympathetic nerve functions and suppression of cardiac output are not directly related to a fall in MAP observed in SHR rats after oxprenolol treatment. Time courses of the hypotensive effect of a single and repeated doses suggest that the accumulation of oxprenolol in active sites which appear to be located in deep compartments is required to develop hypotensive effect.