LONG-TERM INCREASES IN RENAL SYMPATHETIC-NERVE ACTIVITY AND HYPERTENSION

1. Essential hypertensive patients have been characterized by increase d sympathetic nerve activity, increased peripheral vascular tone, decr eased plasma volume and normal cardiac output when compared with normo tensive subjects. Bilateral renal denervation reduces the magnitude or delays the onset of the blood pressure response in numerous models of experimental hypertension regardless of the aetiology of the elevatio n in arterial pressure. 2. Using a servocontrolled intrarenal infusion system, we have elevated intrarenal noradrenaline concentration via i ntermittent renal artery infusion without decreasing renal blood flow as a method of simulating selective elevation of renal sympathetic out flow. 3. Chronic intrarenal adrenergic stimulation increased arterial pressure within 24 h and this hypertension persisted for 28 consecutiv e days. The elevated arterial pressure was not associated with sustain ed increases in plasma renin activity, aldosterone, circulating catech olamines, arginine vasopressin or significant renal vasoconstriction. Urinary sodium excretion was chronically elevated and the dogs remaine d in negative sodium balance for the duration of the intrarenal noradr enaline infusion. 4. After 2 weeks of elevated intrarenal neurotransmi tter coupled with hypertension, renal vascular reactivity to further a drenergic stimulation was significantly increased because the hyperten sion was maintained during continual reductions in the daily dosage of neurotransmitter allowed to be infused by the servocontroller. After only 28 days of noradrenaline infusion, renal vascular hypertrophy dev eloped in vessels from 150-300 pm. 5. We conclude that selective and i ntermittent increases in intrarenal adrenergic neurotransmitter are su fficient to elicit chronic hypertension in the absence of volume expan sion. This intrarenal neuroadrenergic hypertension is closely associat ed with the haemodynamic parameters which characterize a major subset of human essential hypertensives.