Adenosine alters glomerular filtration control by angiotensin II

Abstract

This study was designed to test the hypothesis that high renal levels of adenosine (ADO) may alter glomerular filtration rate (GFR) control by angiotensin II (ANG II). In normal kidneys, ANG II infusion (20 ng X kg-1 X min-1 iv) decreased renal blood flow (RBF) to 61 +/- 3% of control, increased filtration fraction (FF) to 173 +/- 21% of control, and did not change GFR significantly. During intrarenal ADO infusion at a rate of 1.0 mumol/min, ANG II (20 ng X kg-1 X min-1 iv) decreased RBF and GFR to 61 +/- 5 and 64 +/- 6% of control, respectively. After blocking changes in tubuloglomerular feedback by occluding the ureter during mannitol diuresis, ANG II increased stop-flow pressure and postglomerular resistance (RPG) markedly but did not alter preglomerular resistance (RA), suggesting that the direct actions of circulating ANG II are confined primarily to efferent arterioles in the absence of changes in tubuloglomerular feedback. However, during intrarenal ADO infusion and inhibition of tubuloglomerular feedback, ANG II decreased stop-flow ureteral pressure and raised RA and RPG to 213 +/- 27 and 155 +/- 7% of control, respectively, while decreasing RBF to 59 +/- 5% of control. These observations suggest that ADO markedly alters the control of GFR by ANG II, possibly by causing ANG II to constrict preglomerular vessels, an effect that is not apparent in most physiological conditions but which could play a role in lowering GFR when renal ADO and ANG II levels are both elevated, as in severe renal ischemia.

Role of Adenosine A1Receptor in Angiotensin II- and Norepinephrine-Induced Renal Vasoconstriction

“…Consistent with previous reports (Hall and Granger, 1986;Aki et al, 1990), the present data showed that intrarenal infusion of adenosine evoked a transient reduction in renal blood flow that rapidly waned, with renal blood flow returning to a value above the control level. We also observed that renal blood flow was further increased after addition of KW-3902 to adenosine infusion.…”

“…The results from the present study confirm previous observations that renal vasoconstrictor actions of angiotensin II were augmented by intra-arterial infusion of exogenous adenosine in anesthetized dogs (Hall and Granger, 1986). Furthermore, the present data extend these observations to indicate that adenosine also augments norepinephrine-induced renal vasoconstriction.…”

“…Substantial experimental evidence supports the existence of a synergistic interaction between adenosine and the renin-angiotensin system in regulating renal hemodynamics (Hall et al, 1985;Hall and Granger, 1986;Wang et al, 1992;Munger and Jackson, 1994;Navar et al, 1996;Traynor et al, 1998). Early studies showed that suppression of the renin-angiotensin system by feeding a high-sodium diet (Osswald et al, 1975) or administration of an angiotensin-converting enzyme inhibitor (Hall et al, 1985) blunts the renal vasoconstrictor action of adenosine.…”

Renal arteriolar angiotensin responses during varied adenosine receptor activation.

“…3 -3 -911 The proposed role of adenosine is unique among these substances in that local production of this compound is postulated to accentuate rather than attenuate vasoconstrictor responses to Ang II. For example, Hall and Granger 5 reported that intrarenal adenosine infusion alters the influence of Ang II on glomerular function in the dog in a manner consistent with an unmasking of a preglomerular vasoconstrictor effect of Ang II. These investigators proposed that prevailing interstitial adenosine levels may be an important determinant of afferent arteriolar Ang II responsiveness, whereas efferent responses to Ang II appear to be adenosine independent.…”

“…3 - 5 Such observations have led to the suggestion that the effects of Ang II on afferent and/or efferent arterioles might be modulated by the action of an endogenously produced substance. The substances proposed to modulate renal microvascular Ang II responsiveness include vasodilator prostaglandins, 6 -7 endothelium-derived relaxing factor, 8 and adenosine.…”