THE INFLUENCE OF ATROPINE AND ATENOLOL ON THE CARDIAC HEMODYNAMIC-EFFECTS OF NG-NITRO-L-ARGININE METHYL-ESTER IN CONSCIOUS, LONG EVANS RATS

1 In the present study, the extent to which baroreflexes contribute to the cardiac effects of N(G)-nitro-L-arginine methyl ester (L-NAME) was assessed in conscious, Long Evans rats chronically instrumented with thoracic electromagnetic flow probes for the measurement of cardiac haemodynamics. 2 L-NAME (10 mg kg-1, i.v.) was administered in the absence (n = 6) and in the presence (n = 7) of atropine (1 mg kg-1) and atenolol (1 mg kg-1). 3 L-NAME caused a marked increase in mean arterial pressure and marked reductions in total peripheral conductance, cardiac output, heart rate, stroke volume, peak thoracic flow and the maximum rate of rise of aortic flow. 4 Administration of atropine, after the maximal bradycardic effect of L-NAME was established, restored the heart rate to resting levels. Concurrently, there was a reduction in stroke volume, such that cardiac output, although transiently elevated, did not show a sustained increase. No other variables were significantly affected by atropine. Additional administration of atenolol had no effect other than to cause a slight bradycardia, such that in the presence of atropine and atenolol, heart rate was not different from that in animals receiving atropine and atenolol before L-NAME. 5 In the presence of atropine and atenolol, L-NAME had similar pressor, vasoconstrictor and cardiac haemodynamic effects to those in untreated animals, although the bradycardia was significantly attenuated. However, there was still a significant reduction in heart rate following L-NAME in the presence of atropine and atenolol. 6 These results indicate that the major component of the bradycardia following L-NAME is indirect and mediated through an increase in vagal efferent activity. However, the substantial reduction in cardiac function caused by L-NAME is not dependent on the autonomic control of the heart but rather, may depend on the increase in afterload and/or a direct effect of L-NAME on the heart and/or its vasculature.