Effects of selective A1 receptor blockade on glomerular hemodynamics: involvement of renin-angiotensin system.
We examined the renal effects of a specific adenosine A1-receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10 micrograms.kg-1.min-1 iv). Since adenosine is a potent inhibitor of renin release, additional experiments were performed with an angiotensin AT1-receptor antagonist (losartan, 10 mg/kg i.v.). DP CPX alone induced a significant (P < 0.05) decrease in afferent arteriolar resistance (RA, 1.83 +/- 0.18 to 1.43 +/- 0.06 dyn.s.cm-5 x 10(10); P < 0.05). This led to a rise in the transcapillary hydraulic pressure difference (delta P, 35 +/- 1 to 43 +/- 2 mmHg; P < 0.05). Surprisingly, the glomerular capillary ultrafiltration coefficient (Kf) fell (0.101 +/- 0.017 to 0.064 +/- 0.009 nl.s-1.mmHg-1, P < 0.05). Additionally, DPCPX infusion resulted in dramatic increases in both urine flow and sodium excretion. With losartan pretreatment, DPCPX did not cause significant changes in RA and delta P. Also, DPCPX increased Kf (0.057 +/- 0.005 to 0.075 +/- 0.008 nl.s-1.mmHg-1, P < 0.05). Furthermore, the large DPCPX-induced increases in urine flow and sodium excretion were largely suppressed by pretreatment with losartan. These data indicate that endogenous adenosine plays a significant role in maintaining afferent arteriolar tone and that the renin-angiotensin system may mediate some of the wide ranging renal effects of adenosine.
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30022.
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D000241:Adenosine / Q000502:physiology; D000704:Analysis of Variance; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects / Q000502:physiology; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D019808:Losartan; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000502:physiology; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology*
D001713:Biphenyl Compounds; D007093:Imidazoles; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D013777:Tetrazoles; D014970:Xanthines; D000804:Angiotensin II; C051360:1,3-dipropyl-8-cyclopentylxanthine; D019808:Losartan; D000241:Adenosine