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 language | English |
|---|---|
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Volume | 279 |
| Issue number | 2 48-2 |
| Publication status | Published - 2000 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Antihypertensive properties of a nitric oxide-releasing naproxen derivative in two-kidney, one-clip rats
AU - Muscara, M. N.
AU - McKnight, W.
AU - Lovren, F.
AU - Triggle, Christopher
AU - Cirino, G.
AU - Wallace, J. L.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Anti-inflammatory
KW - Endothelin
KW - Prostaglandin
UR - http://www.scopus.com/inward/record.url?scp=0033859325&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033859325&partnerID=8YFLogxK
M3 - Article
C2 - 10924050
AN - SCOPUS:0033859325
VL - 279
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6135
IS - 2 48-2
ER -