Renal vascular responsiveness to angiotensin II at an early stage of diabetes: interaction between intrarenal noradrenergic and renin-angiotensin systems.
The renin-angiotensin system (RAS) has been implicated in haemodynamic maladaptations of diabetic kidney. Its effects may be modulated by endogenous substances like noradrenaline. Our aim was to study renal vascular response to angiotensin II and the interaction between intrarenal RAS and noradrenergic system at an early diabetic stage. Seven days after alloxan induction of diabetes, concentration-response curves to noradrenaline and angiotensin were generated in isolated, perfused rat kidneys. Percent changes in renal vascular resistance were considered as contractile responses. Diabetic kidneys showed enhanced noradrenaline sensitivity compared to controls. Enalapril and losartan elicited increments in ED(50) of noradrenaline in diabetics (diabetic, 3.4+/-0.2 nmol; diabetic + enalapril, 5.1+/-0.5 nmol, p<0.01 vs. diabetic; diabetic + losartan, 5.5+/-0.7 nmol, p<0.05 vs. diabetic). Maximum response (MR) and sensitivity to angiotensin were augmented in diabetics compared to controls. Prazosin decreased MR and sensitivity in diabetics (MR: control, 156.4%+/-5.1%; diabetic, 262.2%+/-21.1%, p<0.001 vs. control; diabetic + prazosin, 178.8%+/-11.2%, p<0.01 vs. diabetic). Enalapril, losartan and prazosin did not change control responses. At this diabetic stage, renal vasculature presented increased response to angiotensin, and an interaction between renal RAS and noradrenergic system was evidenced. Vascular response to noradrenaline requires the integrity of intrarenal RAS and the participation of AT(1) receptors; alpha(1)-adrenoceptors contribute to vascular response to angiotensin.
García
V M C
VM
Pharmacology, Department of Physiological Sciences, Faculty of Pharmaceutical and Biochemical Sciences, National University of Rosario, CONICET, Suipacha 531, 2000, Rosario, Argentina.
Monasterolo
L A
LA
Elías
M M
MM
D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology*; D004656:Enalapril / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D000804:Angiotensin II; D004656:Enalapril; D019808:Losartan; D009638:Norepinephrine