Inhibition of NOS enhances pulmonary vascular changes in stroke-prone spontaneously hypertensive rats.
To determine the effects of chronic nitric oxide (NO) blockade on the pulmonary vasculature, 58-day-old spontaneously hypertensive rats of the stroke-prone substrain (SHRSP) and Wistar-Kyoto rats (WKY) received N(omega)-nitro-L-arginine (L-NNA; 15 mg. kg(-1). day(-1) orally for 8 days). Relaxation to acetylcholine (ACh) in hilar pulmonary arteries (PAs), the ratio of right ventricular (RV) to body weight (RV/BW) to assess RV hypertrophy (RVH), and the percent medial wall thickness (WT) of resistance PAs were examined. L-NNA did not alter the PA relaxation, RV/BW, or WT in WKY. Although the PA relaxation and RV/BW in control SHRSP were comparable to those in WKY, the WT was increased (31 +/- 2 vs. 19 +/- 1%). L-NNA-treated SHRSP showed two patterns: in one group, the relaxation, RV/BW, and WT were comparable to those in the control SHRSP; in the other, impaired relaxation (36 +/- 7 vs. 88 +/- 4% for WKY) was associated with an increase in WT (37 +/- 1%) and RV/BW (0. 76 +/- 0.05). Thus the abnormal pulmonary vasculature in SHRSP at <10 wk of age is not accompanied by impaired relaxation in PAs or RVH; however, impaired relaxation is associated with increased WT and RVH.
Mathew
R
R
Departments of Pediatrics, Pharmacology, and Pathology, New York Medical College, Valhalla, New York 10595, USA. rajamma_mathew@nymc.edu
Fan
N Y
NY
Yuan
N
N
Chander
P N
PN
Gewitz
M H
MH
Stier
C T
CT
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000503:physiopathology; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020022:Genetic Predisposition to Disease; D006976:Hypertension, Pulmonary / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000473:pathology; D017380:Hypertrophy, Right Ventricular / Q000473:pathology; D008168:Lung / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics; D011921:Rats, Inbred WKY; D020521:Stroke / Q000235:genetics*; D014664:Vasodilation
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP