Mechanisms of salt-sensitive hypertension: role of renal medullary inducible nitric oxide synthase.
The goal of this study was to determine the role of renal medullary inducible nitric oxide synthase (iNOS) in the arterial pressure, renal hemodynamic, and renal excretory changes that occur in Dahl/Rapp salt-resistant (R) and salt-sensitive (S) rats during high Na intake. Forty R and S rats, equipped with indwelling arterial, venous, and renal medullary catheters, were subjected to high (8%) Na intake, and selective iNOS inhibition was achieved with continuous intravenous or renal medullary interstitial infusion of aminoguanidine (AG; 3.075 mg. kg(-1). h(-1)). After 5 days of AG, mean arterial pressure increased to 132 +/- 2% control in the S rats with high Na intake and intramedullary AG compared with 121 +/- 4% control (P < 0.05) in the S rats with high Na intake alone and 121 +/- 2% control (P < 0.05) in the S rats with high Na intake and intravenous AG. AG did not change arterial pressure in R rats. AG also caused little change in renal hemodynamics, urinary Na, or H(2)O excretion or ACh-induced aortic vasorelaxation in R or S rats. The data suggest that during high Na intake, nitric oxide produced by renal medullary iNOS helps to prevent excessive increases in arterial pressure in the Dahl S rat but not the R rat.
Tian
Niu
N
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.
Gannon
Anthony W
AW
Khalil
Raouf A
RA
Manning
R Davis
RD
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000201:enzymology* / Q000503:physiopathology*; D007679:Kidney Medulla / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D020303:Rats, Inbred Dahl; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000008:administration & dosage / Q000494:pharmacology* / Q000652:urine; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects
D006146:Guanidines; D009569:Nitric Oxide; D012964:Sodium; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine