Modulation of endothelin-1 coronary vasoconstriction in spontaneously hypertensive rats by the nitric oxide system

Am J Hypertens. 2000 Jan;13(1 Pt 1):83-7. doi: 10.1016/s0895-7061(99)00100-4.

Abstract

To determine whether nitric oxide contributes to the augmented vasoconstrictive response to endothelin-1 (ET-1) in coronary vessels of hypertensive hearts, and also whether L-arginine administration can inhibit the augmented response to ET-1, we designed experiments to measure coronary perfusion resistance in isolated hearts of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) with or without L-arginine administration (0.5 g/L) for 2 weeks. The hearts were paced at a constant rate and perfused by the Langendorff technique at constant pressure (75 mm Hg). Perfusion flow and pressure were monitored, and coronary vascular resistance (CVR) was calculated. ET-1 infusion elicited dose-dependent increases in CVR in both WKY and SHR. At an ET-1 concentration of 1.5 x 10(-9) mol/L, the response was significantly greater in SHR. In L-NAME-treated WKY and SHR, responses to ET-1 were augmented, compared with those of nontreated rats, and this augmentation was greater in WKY. L-arginine administration reduced the CVR response to ET-1 in SHR, whereas it did not change responses to ET-1 in WKY. These findings suggest that the augmented vasoconstriction of the coronary artery induced by ET-1 in hypertensive hearts was due to a reduction in nitric oxide release in coronary vessels and that L-arginine can partially inhibit the vasoconstrictive response of the coronary artery.

MeSH terms

  • Animals
  • Arginine / pharmacology
  • Blood Pressure / drug effects
  • Coronary Vessels / drug effects*
  • Endothelin-1 / antagonists & inhibitors
  • Endothelin-1 / pharmacology*
  • Enzyme Inhibitors / pharmacology
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase Type III
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Vasoconstriction / drug effects*

Substances

  • Endothelin-1
  • Enzyme Inhibitors
  • Nitric Oxide
  • Arginine
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • NG-Nitroarginine Methyl Ester