Nitric oxide in the renal medulla protects from vasopressin-induced hypertension.
In the present study, we assessed whether activation of the nitric oxide (NO) system within the renal medulla could serve as a buffer against the chronic hypertensive effects of arginine vasopressin (AVP). NO concentration in the renal medulla of Sprague-Dawley rats was measured with in vivo microdialysis/oxyhemoglobin NO trapping. The results showed that medullary interstitial [NO] was increased after 2 hours of AVP infusion and remained elevated even after 10 days (by 62+/-8% and 42+/-13%, respectively). Western blot analysis showed that 2 days of AVP infusion was insufficient to increase protein expression of any of the NO synthase (NOS) isoforms, but after 10 days of AVP infusion, endothelial NOS expression was significantly increased in the inner medulla with no significant changes in noninducible NOS and inducible NOS levels. When renal medullary NOS enzyme activity was blunted with a nonpressor dose of N(G)-nitro-L-arginine methyl ester (75 microg. kg(-1). h(-1)) that was chronically infused locally into the renal medulla, intravenous AVP infusion (which was shown earlier to be subpressor in chronic studies) produced a sustained elevation in arterial pressure (from 107+/-2 to 121+/-2 mm Hg). These data indicate that chronic elevations in plasma AVP enhance renal medullary endothelial NOS protein expression, which enables sustained elevations of NO concentrations in this region of the kidney to buffer the hypertensive effects of AVP.
Szentiványi
M
M
Clinical Research Department-2nd Institute of Physiology, Semmelweis University of Medicine, Budapest, Hungary.
Park
F
F
Maeda
C Y
CY
Cowley
A W
AW
D000818:Animals; D001120:Arginine / Q000378:metabolism; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006977:Hypertension, Renal / Q000139:chemically induced / Q000378:metabolism*; D007262:Infusions, Intravenous; D007679:Kidney Medulla / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017207:Rats, Sprague-Dawley; D012076:Renal Agents / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D012076:Renal Agents; D001127:Arginine Vasopressin; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019331:NG-Nitroarginine Methyl Ester