Jl. Osborn et al., LONG-TERM INCREASES IN RENAL SYMPATHETIC-NERVE ACTIVITY AND HYPERTENSION, Clinical and experimental pharmacology and physiology, 24(1), 1997, pp. 72-76
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.