Decreased chronotropic responses to adrenergic stimulation following sinoaortic denervation in the rat.

The present experiments were designed to study the mechanisms involved in the normalization of the resting heart rate (HR) of sino-aortic denervated (SAD) rats when hypertension persisted. Under conscious resting conditions, 50 SAD-n (rats whose HR had returned to normal, 374 +/- 5 beats/min, after transitory tachycardia) had mean arterial pressure (MAP) higher than that of 34 sham-operated (SO) rats (132 +/- 2 vs 109 +/- 1 mmHg), while 25 SAD-t (rats with tachycardia, 450 +/- 6 beats/min, 5 hours after SAD) had even higher MAP (151 +/- 2 mmHg). The SAD-n rats had less intense tachycardia in response to stress (acoustic stimuli and tail pinching) than the SO-rats. Within the first 5-6 days following SAD the rats showed a marked decrease in food and water consumption. Chloralose anesthesia, rather than urethane or chloralose plus urethane, was selected for the acute experiments because the HR, after an initial increase, remained stable at approximately the same values observed before anesthetization, provided the decrease in body temperature was compensated. Sympathetic tone, vagal tone and "intrinsic HR" were evaluated in the anesthetized rats by the autonomic blockade produced by atropine and propranolol. Tachycardia (437 +/- 10 beats/min) in the SAD-t rats was accompanied by normal "intrinsic" HR (381 +/- 6 vs 389 +/- 9 beats/min in SO-rats) and elevated sympathetic tone (85 +/- 11 vs 29 +/- 5 beats/min in SO-rats). In the SAD-n rats the "intrinsic" HR was reduced (362 +/- 3 beats/min) and the sympathetic tone depressed (16 +/- beats/min). Vagal tone showed a small but not significant decrease in both SAD-t and SAD-n (16 +/- 7 and 20 +/- 4 beats/min below "intrinsic" HR, respectively, vs 33 +/- 5 in the SO-rats). The SAD-t and SAD-n rats had decreased chronotropic responses to infusion of increasing doses of isoproterenol. The threshold doses needed to produce tachycardia were 16 times higher than in the SO-rats. The data suggest that desensitization of the beta-adrenoceptors after a long period of sympathetic stimulation probably contributed significantly to the normalization of the HR, to the reduced sympathetic tone and to the less intense tachycardia response to stress exhibited by the SAD-n rats.