Vasodilator effect of human adrenomedullin(13 – 52) on hypertensive rats

1995 ◽  
Vol 73 (7) ◽  
pp. 1065-1069 ◽  
Author(s):  
Q. Tian ◽  
D. Zhao ◽  
D. Y. Tan ◽  
Y. T. Zhao ◽  
Q. H. Li ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Molecular Mechanisms ◽  
Hypotensive Activity ◽  
Hypertensive Rats ◽  
Hypotensive Action ◽  
Spontaneously Hypertensive ◽  
Endothelin 1 ◽  
In Vitro Effects

Human adrenomedullin (hADM) is a newly isolated peptide with hypotensive activity in normotensive rats. The objective of this study was to investigate the effect of hADM(13–52) on hypertensive animals. hADM(13–52) induced a dose-dependent decrease in the blood pressure of spontaneously hypertensive rats and renal hypertensive rats. This result suggests that hADM is a novel antihypertensive peptide. In isolated rat aortic arteries, hADM(13–52) produced nitric oxide dependent relaxation and inhibited endothelin 1 and angiotensin II release. These in vitro effects may represent the molecular mechanisms underlying the hypotensive action of hADM in vivo.Key words: human adrenomedullin, nitric oxide, endothelin 1, angiotensin II, hypertension.

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

2000 ◽  
Vol 279 (2) ◽  
pp. H528-H535 ◽  
Author(s):  
Marcelo N. Muscará ◽  
Webb McKnight ◽  
Fina Lovren ◽  
Christopher R. Triggle ◽  
Giuseppe Cirino ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Renal Artery ◽  
Hypertensive Rats ◽  
Endothelin 1 ◽  
Inflammatory Drugs ◽  
Nitric Oxide Releasing ◽  
Antihypertensive Properties ◽  
Hypotensive Response

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.

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