Antihypertensive properties of a nitric oxide-releasing naproxen derivative in two-kidney, one-clip rats

M. N. Muscara, W. McKnight, F. Lovren, Christopher Triggle, G. Cirino, J. L. Wallace

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Nonsteroidal anti-inflammatory drugs have been reported to exacerbate hypertension. In this study, we tested the hypothesis that a nitric oxide-releasing derivative of naproxen would ameliorate hypertension in the rat. Hypertension was induced by partially occluding one renal artery (the '2K, 1C' model), and 2 wk later the rats started receiving naproxen, the nitric oxide-releasing derivative HCT-3012, or vehicle each day for 2 wk. Naproxen significantly exacerbated the hypertension. HCT-3012 significantly reduced blood pressure relative to both the naproxen- and vehicle-treated groups. Both naproxen and HCT-3012 markedly suppressed whole blood thromboxane B2 synthesis. In studies of anesthetized rats, naproxen significantly enhanced the late hypertensive response to endothelin-1 and significantly blunted the early hypotensive response. In contrast, HCT-3102 did not affect either response to endothelin-1. In vitro, HCT-3012 significantly reduced the responsiveness of aortic rings to the contractile effects of phenylephrine. These studies suggest that HCT-3012 reduces blood pressure in hypertensive rats, not simply through the vasodilatory actions of the nitric oxide it releases, but through alterations in the responsiveness of the vasculature to endogenous pressor agents.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume279
Issue number2 48-2
Publication statusPublished - 2000
Externally publishedYes

Fingerprint

Naproxen
Surgical Instruments
Antihypertensive Agents
Kidney
Hypertension
Endothelin-1
Blood Pressure
Thromboxane B2
Phenylephrine
Renal Artery
Nitric Oxide
Anti-Inflammatory Agents
HCT 3012
naproxen-n-butyl nitrate
Pharmaceutical Preparations

Keywords

  • Anti-inflammatory
  • Endothelin
  • Prostaglandin

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Antihypertensive properties of a nitric oxide-releasing naproxen derivative in two-kidney, one-clip rats. / Muscara, M. N.; McKnight, W.; Lovren, F.; Triggle, Christopher; Cirino, G.; Wallace, J. L.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 279, No. 2 48-2, 2000.

Research output: Contribution to journalArticle

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