Adrenergic mechanisms in human hypertension and in spontaneously hypertensive rats.
1. The role of adrenergic neuronal mechanisms in the development of early hypertension in man and the spontaneously hypertensive rat has been explored. 2. In both, a hyperkinetic circulatory state is associated with reduced parasympathetic and increased adrenergic cardiac influences. 3. Spontaneously hypertensive and normotensive control rats were treated with propranolol from conception until 12 weeks. Although heart rate and output remained reduced, there was no difference in growth or elaboration of pressure with respect to their untreated controls. 4. After another series of spontaneously hypertensive and control rats received cardiac autonomic blockade (atropine and timolol), they sequentially received alpha-adrenergic blockade (phenoxybenzamine), ganglionic blockade (trimethaphan) and smooth-muscle vasodilatation (hydralazine). These studies revealed only a small pressure differential between the two groups before hydralazine and still less thereafter; unlike the control rats, pressure in spontaneously hypertensive rats fell markedly after ganglionic blockade as a result of reduced output, indicating greater adrenergic control mediated through venoconstriction. 5. These findings indicate: increased cardiovascular adrenergic control in young spontaneously hypertensive rats, the hyperkinetic circulation merely reflecting one aspect of increased total cardiovascular input. Structural alterations seem to participate minimally. 6. These experimental observations closely, resemble findings in early hypertensive man, and it is suggested that altered total cardiovascular adrenergic input is responsible for the elaboration, development, and maintenance of essential hypertension in man.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000235:genetics; D008297:Male; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D013564:Sympathetic Nervous System / Q000502:physiology*; D013999:Timolol / Q000494:pharmacology; D014294:Trimethaphan / Q000494:pharmacology
D010643:Phenoxybenzamine; D014294:Trimethaphan; D001285:Atropine; D013999:Timolol