Balance among autonomic controls of heart rate in neonatal spontaneously hypertensive and borderline hypertensive rats.

Abstract

The ontogeny of functional sympathetic neural, adrenal medullary, and extra-adrenal components of adrenergic control of heart rate was compared in neonatal Spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) and Borderline hypertensive (BHR) rats using combined sequential pharmacological blockade and surgical intervention. Baseline heart rate recorded from awake and unrestrained pups was lower in BHR than in WKY or SHR at 5 days of age. Tonic sympathetic neural control of heart rate was inferred from bradycardia after treatment with the adrenergic neuron-blocking agent, bretylium tosylate. Bradycardia after bretylium treatment was observed at 2, 5 and 8 days of age in all strains, suggesting tonic sympathetic neural control of heart rate during the first postnatal week. Parasympathetic control of heart rate was inferred from heart rate increase after treatment with the muscarinic receptor blocker, atropine methyl nitrate, in pups pretreated with bretylium. Tachycardia following atropine methyl nitrate was substantial in all 24-day-old pups. Control of heart rate by neurally mediated release of catecholamines from the adrenal medulla was inferred from bradycardia following administration of the ganglionic blocking agent, hexamethonium, to pups pretreated with bretylium and atropine methyl nitrate. Heart rate decreases after hexamethonium were found in 2-day-old WKY and BHR pups, and at 5 and 8 days in all strains. Adrenalectomy was performed in additional animals to confirm the adrenal catecholamine influence on heart rate. The influence of residual circulating catecholamines on neonatal heart rate was inferred from bradycardia following administration of the beta-adrenergic receptor blocking agent, atenolol, in pups pretreated with bretylium, methylatropine, and hexamethonium. Bradycardia was observed in pups of each strain and at all ages after atenolol treatment. Strain differences in autonomic controls of heart rate were most pronounced at 24 days of age. At 24 days of age both SHR and BHR pups showed increased adrenal catecholamine and parasympathetic influences on heart rate compared to WKY. Thus, prior to weaning, rats differing in their genetic predisposition to hypertension showed a unique pattern of autonomic control over heart rate which may be related to adult cardiovascular regulation.