Impaired Vasoconstrictor Nerve Function in Spontaneously Hypertensive Rats after Long-Term Treatment with Propranolol and Metroprolol

Abstract

The neuroeffector function of the portal vein from spontaneously hypertensive rats (SHR) was studied in vitro 2 days after cessation of long-term exposure to the .beta.-receptor blocking drugs propanolol and metoprolol. Smooth muscle responses to vasomotor nerve stimulation and to exogenous noradrenaline (NA) were tested and compared to those of preparations from matched SHR controls. The mean arterial pressure levels of the propranolol-treated and metoprolol-treated groups of rats were 124 .+-. 13 mm Hg and 134 .+-. 4 mm Hg, respectively, and were significantly lower than the value for the control group, 153 .+-. 4 mm Hg. The sensitivity of the portal vein to exogenous NA was not altered in the treated animals. Neither the maximum tension response to NA, nor the magnitude of the inhibitory response to isoprenaline (1 .mu.M) of portal vein preparations from animals treated with the .beta.-receptor antagonists, differed from control values. A significant difference was observed in the TNS (2-p-toluidinylnapthalene-6-sulfonate) frequency-response relationships. Preparations from propranolol-treated animals responded less than their controls to each frequency of postganglionic nerve stimulation particularly at low impulse rates (.ltoreq. 4 Hz) where individual responses were depressed by approximately 50%. Prolonged treatment of the SHR with metoprolol led to a statistically significant suppression of the neurogenic responses at low, physiological impulse rates, whereas maximum response to TNS, was not consistently suppressed. Prolonged administration of propranolol and metoprolol resulted in lower blood pressure levels in treated animals than in the control group of SHR. The demonstrated anti-hypertensive effect is probably due to .beta.-receptor blockade. The present findings should be relevant to the clinical situation.