Effect of nitric oxide on renal autoregulation during hypothermia in the rat.
Hypothermia-induced reduction of metabolic rate is accompanied by depression of both glomerular perfusion and filtration. The present study investigated whether these changes are linked to changes in renal autoregulation and nitric oxide (NO) signalling. During hypothermia, renal blood flow (RBF) and glomerular filtration rate (GFR) were reduced and urine production was increased, and this was linked with reduced plasma cGMP levels and increased renal vascular resistance. Although stimulation of NO production decreased vascular resistance, blood pressure and urine flow, intravenous infusion of the NO precursor L-arginine or the NO donor sodium nitroprusside did not alter RBF or GFR. In contrast, inhibition of NO synthesis by Nw-nitro-L-arginine led to a further decline in both parameters. Functional renal autoregulation was apparent at both temperatures. Below the autoregulatory range, RBF in both cases increased in proportion to the perfusion ±pressure, although, the slope of the first ascending limb of the pressure-flow relationship was lower during hypothermia. The main difference was rather that the curves obtained during hypothermia levelled off already at a RBF of 3.9 ± 0.3 mL/min then remained stable throughout the autoregulatory pressure range, compared to 7.6 ± 0.3 mL/min during normothermia. This was found to be due to a threefold increase in, primarily, the afferent arteriolar resistance from 2.6 to 7.5 mmHg min mL-1. Infusion of sodium nitroprusside did not significantly affect RBF during hypothermia, although a small increase at pressures below the autoregulatory range was observed. In conclusion, cold-induced rise in renal vascular resistance results from afferent arteriolar vasoconstriction by the autoregulatory mechanism, setting RBF and GFR in proportion to the metabolic rate, which cannot be explained by reduced NO production alone.
ECMO Centre Karolinska, Department of Pediatric Perioperative Medicine and Intensive Care, Karolinska University Hospital, 171 76, Stockholm, Sweden. lars.broman@karolinska.se.|Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden. lars.broman@karolinska.se.|Department of Medical Cell Biology, Section for Physiology, Uppsala University, 751 23, Uppsala, Sweden. lars.broman@karolinska.se.
Lars Mikael
0000-0003-4124-4581
LM
Broman
Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden. mattias.carlstrom@ki.se.
Mattias
M
Carlström
Department of Medical Cell Biology, Section for Physiology, Uppsala University, 751 23, Uppsala, Sweden.
Örjan
Ö
Källskog
Department of Medical Cell Biology, Section for Physiology, Uppsala University, 751 23, Uppsala, Sweden.
Mats
M
Wolgast
D000818:Animals; D005919:Glomerular Filtration Rate; D006706:Homeostasis; D007035:Hypothermia / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism / Q000502:physiology* / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D014655:Vascular Resistance
D009569:Nitric Oxide
Autoregulation; GFR; Hypothermia; Nitric oxide; Renal blood flow; Vascular resistance