Norepinephrine overflow and renin pattern of the individual kidney in patients with unilateral renal artery stenosis.

Abstract

This study was performed to determine divided renal efferent sympathetic nerve activity from kidneys in seven patients with renin-positive, unilateral renal artery stenosis before and 30 minutes after an acute intravenous dose of 125 mg enalaprilaL Renal norepinephrine release was calculated from split renal plasma flow, venoarterial plasma concentration gradients across the kidney, and the fractional extraction of tritiated norepinephrine. All patients had unilateral renin secretion, the affected kidney increasing its plasma renin activity gradient 1.7-fold, whereas no statistically significant change was noted on the contralateral side in response to enalaprilat. Total norepinephrine release to plasma and norepinephrine plasma clearance (assessed by isotope dilution) were similar before and after administration of enalaprilat (approximately 400 ng/min and 1.0 I/min), despite a 26% fall in mean arterial pressure (from 125 mm Hg, /><0.01). Heart rate remained unchanged. After enalaprilat, norepinephrine venoarterial difference increased in the renin-secreting kidney (from 264 to 396, SED=57 pg/ml,p<0.05), whereas it increased only slightly in the contralateral kidney (from 149 to 256, SED=72 pg/mJ, NS). Tritiated norepinephrine extraction fell approximately 25% (/?<0.01) in both kidneys. Thus, renal norepinephrine spillover increased from 49 to 62, SED=9 ng/min (NS) and from 81 to 129, SED=17 ng/min (p<0.05) from the affected and the contralateral kidney, respectively. Hence, in this relatively small study in patients with renovascular hypertension, no evidence for increased renal nerve activity could be observed in the affected kidney, despite its marked renin production. Furthermore, it appears that angiotensin converting enzyme inhibition may influence renal neuronal uptake of norepinephrine, as enalaprilat reduced fractional extraction of norepinephrine. (Hypertension 1991;17:1003-1009) I t generally is believed that the renin-angiotensin system plays an important role in renal hypertension.1 -2 The involvement of the sympathetic nervous system, however, is less clear. Direct recording of muscle sympathetic nerve activity has been reported to be elevated in patients with renal artery stenosis compared with controls.3 This increase was normalized after percutaneous transluminal angioplasty on the affected renal artery.3 Although increased muscle sympathetic nerve activity may prevail in renovascular hypertension, 3 the possible involvement of the renal nerves is less clear.Studies of the sympathetic nervous system by measurements of norepinephrine (NE) have yielded increased levels of NE in the renal vein both during resting conditions 4 and in response to acute blood pressure reduction by hydralazine in patients with unilateral renal artery stenosis. 56 Moreover, Gordon et al 7 showed increased levels of NE in left adrenal vein in humans with renal hypertension on the basis of renal artery stenosis. These findings have been taken as evidence for an increased renal sympathetic nerve activity. 56 The experim...

Angiotensin II exerts differential actions on renal nerve activity and heart rate.

“…The curve relating RSNA to MAP during infusions of graded doses of Ang II was identical to that during infusions of graded doses of phenylephrine, suggesting that the Ang II-induced reduction in RSNA was simply a reflex response to the increase in arterial pressure. Although it has been reported that the activity of the sympathetic nervous system did not increase during Ang II infusion in humans as assessed by measurement of norepinephrine spillover 19 or renal norepinephrine release, 20 the present results provide direct evidence that Ang II does not increase RSNA. Indeed, the results indicate that the pressor response to Ang II is buffered by a decrease in RSNA.…”

Testosterone Effects on Renal Norepinephrine Content and Release in Rats With Different Y Chromosomes

“…It has been proposed that angiotensin II interacts with the SNS to facilitate NE release in the kidney. 45 Renal denervation has been shown to delay the onset or decrease the severity of renal hypertension 46,47 and results in a major reduction in renal NE content in SHR and WKY. 47 Dihydrotestosterone also has been shown to have a tissue-specific regulation of renin mRNA in several organs important for blood pressure control, eg, the kidney, adrenal gland, and brain in female mice.…”

Are Centrally Acting Imidazoline Agents Appropriate Therapy for Renovascular Hypertension?

“…The advantage of the noradrenaline spillover technique is that it has been possible to sample from regional veins and gauge an estimation of sympathetic activity to a variety of organs independently. In a relatively small study in patients with renovascular hypertension, Friberg and colleagues24 found no evidence for increased renal nerve activity in the affected kidney, despite the marked renin production. Another study from this group, however, has shown an increased sympathetic activity to the heart in patients with renovascular hypertensive patients 23.…”