Interactions between nitric oxide and renal nerves in the excretion of a saline load in obese Zucker rats.
The present study investigated the potential role of nitric oxide (NO) and its interaction with renal sympathetic nerves in modulating the excretory responses to an acute saline volume expansion (VE), of 10% of body weight, in the innervated and denervated kidneys of both lean and obese Zucker rats. This was done using the NO synthase inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME), 7-nitroindazole and aminoguanidine. In lean rats, cumulative urinary sodium excretion (cuU(Na)V) after 40 min of VE in the innervated kidney was enhanced by 48% in L-NAME-treated rats compared with that in untreated rats, but this was not the case for the denervated kidney. VE in untreated obese rats raised cuU(Na)V to a lesser extent than in the untreated lean rats, by 36% and 46% in the denervated and innervated kidneys respectively (both P<0.001). L-NAME treatment of obese rats increased cuU(Na)V after VE compared with that in untreated obese rats, by 48% in the denervated kidney and by 136% in the innervated kidney (both P<0.001). The magnitude of cuU(Na)V after VE in both kidneys of 7-nitroindazole-treated obese rats was not different from that in untreated obese rats. However, cuU(Na)V was raised (P<0.01) by 56% in the innervated, but not the denervated, kidney of aminoguanidine-treated obese rats. These data show that NO is partially involved in mediating the reflex renal responses to VE in Zucker rat strains. NO, possibly generated by endothelial NO synthase, exerts its effects in obese rats through a renal-nerve-independent mechanism, while the effect of NO generated by inducible NO synthase requires intact renal innervation.
Wongmekiat
O
O
Department of Physiology, Medical School, University of Birmingham, Birmingham B15 2TT, U.K.
Johns
E J
EJ
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004231:Diuresis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007191:Indazoles / Q000494:pharmacology; D007668:Kidney / Q000294:innervation* / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009318:Natriuresis / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D009765:Obesity / Q000503:physiopathology*; D051381:Rats; D011924:Rats, Zucker
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D006146:Guanidines; D007191:Indazoles; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C004479:pimagedine; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester