Increasing animal evidence support an important facilitatory interaction between angiotensin II and norepinephrine within the kidney. This angiotensin II/norepinephrine interaction was investigated in man by examining the effect of enalapril pretreatment (5 mg for 5 days) on the renal response to a low non-pressor dose of intravenous tyramine 4 micrograms/kg/min for 120 min in 8 healthy subjects undergoing water diuresis. Tyramine is an indirect sympathomimetic agent which causes neuronal release of norepinephrine. Enalapril and tyramine, alone and in combination, had no effect on glomerular filtration, effective renal plasma flow or sodium excretion. Tyramine caused a significant increase in urinary flow rate (p < 0.05) but this was not influenced by enalapril pretreatment. The lack of effect of enalapril on the renal response to tyramine contrasts with a previous study which examined the effect of enalapril on the renal response to circulating norepinephrine. This may suggest that enalapril affect renal function only when there is renal vasoconstriction (as with norepinephrine) and not when renal blood flow is unchanged (as with tyramine).
An antisense oligodeoxynucleotide (As-ODN) to the 3' untranslated region of the mRNA sequence expressing the intracellular adhesion molecule-1 (ICAM-1) was employed to determine ICAM-1's role in renal ischaemia-reperfusion injury in the rat. Wistar-Kyoto rats receiving i.v. either lipofectin-As-ODN (As-ODN group), lipofectin-reverse ODN (Rv-ODN group) or lipofectin (ischaemia control group) 8 h prior to study were anaesthetized and subjected to 30 min of renal artery occlusion. Renal haemodynamic and excretory parameters were monitored before and after renal ischaemia. On termination of the study renal tissue was subjected to histological and Western blot analysis. Renal blood flow decreased in the 3 h post-ischaemia period in the ischaemia control and Rv-ODN groups, but was maintained in the As-ODN group. Glomerular filtration rate was depressed initially but gradually increased to 10% above basal levels in the ischaemia control and Rv-ODN groups, but was below basal levels (20%) in the As-ODN group. There was a three- to fourfold increase in sodium and water excretion following ischaemia in the ischaemia control and reverse-ODN groups but not in the As-ODN treated group. The As-ODN ameliorated the histological evidence of ischaemic damage and reduced ICAM-1 protein levels to a greater extent in the medulla than cortex. These observations suggested that in the post-ischaemic period afferent and efferent arteriolar tone was increased with a loss of reabsorptive capacity which was in part due to ICAM-1. The possibility arises that the action of ICAM-1 at vascular and tubular sites in the deeper regions of the kidney contributes to the ischaemia-reperfusion injury.
1 This study was undertaken to characterize the renal responses to acute unilateral renal denervation in anaesthetized spontaneously hypertensive rats (SHR) by examining the effect of acute unilateral renal denervation on the renal hemodynamic responses to a set of vasoactive agents and renal nerve stimulation. 2 Twenty-four male SHR rats underwent acute unilateral renal denervation and the denervation was confirmed by significant drop (P < 0.05) in renal vasoconstrictor response to renal nerve stimulation along with marked diuresis and natriuresis following denervation. After 7 days treatment with losartan, the overnight fasted rats were anaesthetized (sodium pentobarbitone, 60 mg kg(-1) i.p.) and renal vasoconstrictor experiments were performed. The changes in the renal vasoconstrictor responses were determined in terms of reductions in renal blood flow caused by renal nerve stimulation or intrarenal administration of noradrenaline, phenylephrine, methoxamine and angiotensin II. 3 The data showed that there was significantly (all P < 0.05) increased renal vascular responsiveness to the vasoactive agents in denervated rats compared to those with intact renal nerves. In losartan-treated denervated SHR rats, there were significant (all P < 0.05) reductions in the renal vasoconstrictor responses to neural stimuli and vasoactive agents as compared with that of untreated denervated SHR rats. 4 The data obtained in denervated rats suggested an enhanced sensitivity of the alpha(1)-adrenoceptors to adrenergic agonists and possible increase of AT(1) receptors functionality in the renal vasculature of these rats. These data also suggested a possible interaction between sympathetic nervous system and renin-angiotensin system in terms of a crosstalk relationship between renal AT(1) and alpha(1)-adrenoceptor subtypes.