Renal baroreceptor-stimulated renin in the eNOS knockout mouse.
The role of endothelium-derived nitric oxide (NO) in renal baroreceptor stimulation of renin was tested comparing endothelial nitric oxide synthase (eNOS)-deficient mice with C57BL/6J (C57) controls. We measured blood pressure, renal blood flow (RBF), and plasma renin concentration (PRC) in Inactin-anesthetized mice. Blood pressure in eNOS knockout mice was higher than in controls (100 +/- 3 vs. 86 +/- 1 mmHg, respectively; P < 0.001), but RBF was similar (1.71 +/- 0.06 vs. 1.66 +/- 0.09 ml. min(-1). 100 mg kidney wt(-1), respectively), so that renal vascular resistance was also higher in the knockouts (59.81 +/- 2.07 vs. 51.81 +/- 2.66 resistance units, respectively; P < 0.025). PRC was similar (8.24 +/- 1.57 in eNOS knockouts vs. 7.10 +/- 1.19 ng ANG I. ml(-1). h(-1) in C57). NOS inhibition with nitro-L-arginine methyl ester (L-NAME) in C57 controls increased blood pressure (from 85 +/- 2 to 106 +/- 1 mmHg, P < 0.001) and decreased RBF (from 1.66 +/- 0.09 to 1.08 +/- 0.02; P < 0.005), but L-NAME had no effect in eNOS knockout mice. When renal perfusion pressure was reduced in C57 controls to 55 mmHg, PRC increased from 6.6 +/- 0.9 to 14.5 +/- 1.9 microg. ml(-1). h(-1) (P < 0.025), but this response was blocked by L-NAME. However, in eNOS knockouts, reduced renal perfusion pressure increased PRC from 7.6 +/- 1.4 to 15.0 +/- 2.8 microg. ml(-1). h(-1) (P < 0.001). Thus in the chronic absence of eNOS, blood pressure was elevated, but RBF was normal. Additionally, the absence of eNOS did not modify baroreceptor-stimulated renin, suggesting that eNOS-derived NO does not directly mediate this renin-regulating pathway.
Beierwaltes
William H
WH
Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit Medical Campus of Case Western Reserve School of Medicine, Detroit, Michigan 48202, USA.
Potter
D'Anna L
DL
Shesely
Edward G
EG
D000818:Animals; D004727:Endothelium / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007606:Juxtaglomerular Apparatus / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010641:Phenotype; D011311:Pressoreceptors / Q000502:physiology*; D012079:Renal Circulation / Q000502:physiology; D012083:Renin / Q000378:metabolism*; D014661:Vasoconstriction / Q000502:physiology
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D012083:Renin; D019331:NG-Nitroarginine Methyl Ester