Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

Development and Mechanism of a Specific Supersensitivity to Nitrovasodilators After Inhibition of Vascular Nitric Oxide Synthesis in vivo

S. Moncada, D. D. Rees, R. Schulz and R. M. J. Palmer
Proceedings of the National Academy of Sciences of the United States of America
Vol. 88, No. 6 (Mar. 15, 1991), pp. 2166-2170
Stable URL: http://www.jstor.org/stable/2356341
Page Count: 5
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Development and Mechanism of a Specific Supersensitivity to Nitrovasodilators After Inhibition of Vascular Nitric Oxide Synthesis in vivo
Preview not available

Abstract

The mechanism of the increased sensitivity to nitrovasodilators after removal of endothelial nitric oxide (NO) was investigated in vitro and in vivo. The vasoconstrictor potency of phenylephrine and the force of contraction of rat isolated aortic rings were significantly enhanced after endothelium removal or treatment with inhibitors of endothelial NO synthase. Furthermore, these procedures led to a significant decrease in the basal levels of cGMP in the vascular rings. Moreover, the potency of glyceryl trinitrate (n3Gro) and sodium nitroprusside (SNP) as relaxing agents and the ability of SNP to induce increases in cGMP in aortic rings were significantly enhanced in those rings denuded of endothelium or treated with the inhibitors. These procedures did not affect the vasodilator actions of isoprenaline or 8-bromo-cGMP. In the anesthetized rat, treatment with the inhibitors enhanced significantly the hypotensive responses to n3Gro without affecting those to isoprenaline. These data indicate that the removal of the basal NO-mediated vasodilator tone in the cardiovascular system leads, at the level of the soluble guanylate cyclase, to a specific supersensitivity to nitrovasodilators in vivo. The existence of such a phenomenon has important implications for understanding the local physiological control of blood flow, its pathological disturbances, and the mechanism of action of nitrovasodilators.

Page Thumbnails

  • Thumbnail: Page 
2166
    2166
  • Thumbnail: Page 
2167
    2167
  • Thumbnail: Page 
2168
    2168
  • Thumbnail: Page 
2169
    2169
  • Thumbnail: Page 
2170
    2170