Inhibition of NOS enhances pulmonary vascular changes in stroke-prone spontaneously hypertensive rats

Am J Physiol Lung Cell Mol Physiol. 2000 Jan;278(1):L81-9. doi: 10.1152/ajplung.2000.278.1.L81.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Blood Vessels / drug effects
  • Blood Vessels / physiopathology
  • Cyclic AMP / physiology
  • Cyclic GMP / physiology
  • Endothelium, Vascular / physiopathology
  • Enzyme Inhibitors / pharmacology
  • Genetic Predisposition to Disease*
  • Hypertension, Pulmonary / genetics*
  • Hypertension, Pulmonary / pathology
  • Hypertension, Pulmonary / physiopathology*
  • Hypertrophy, Left Ventricular / pathology
  • Hypertrophy, Right Ventricular / pathology
  • Lung / pathology
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitroarginine / pharmacology
  • Pulmonary Circulation* / drug effects
  • Rats
  • Rats, Inbred SHR / genetics
  • Rats, Inbred WKY
  • Stroke / genetics*
  • Vasodilation

Substances

  • Enzyme Inhibitors
  • Nitroarginine
  • Cyclic AMP
  • Nitric Oxide Synthase
  • Cyclic GMP