Losartan reduces constrictor responses to endothelin‐1 and the thromboxane A2analogue in aortic rings from spontaneously hypertensive ratsrole of nitric oxide
作者:
Rosaura Maeso,
Elena Rodrigo,
Raquel Muñoz-García,
Josefa Navarro-Cid,
Luis Ruilope,
Vicente Lahera,
Victoria Cachofeiro,
期刊:
Journal of Hypertension
(OVID Available online 1997)
卷期:
Volume 15,
issue 12
页码: 1677-1684
ISSN:0263-6352
年代: 1997
出版商: OVID
关键词: angiotensin II receptor antagonist;angiotensin-converting enzyme inhibitors;nitric oxide;endothelin;thromboxane A2;spontaneous hypertensive rats
数据来源: OVID
摘要:
ObjectiveOur study was designed to investigate whether angiotensin II subtype 1 (AT1) receptors are involved in the constrictor responses evoked by endothelin-1 and the thromboxane A2analogue U46619 in aortic rings from spontaneously hypertensive rats (SHR), by studying the effect of the AT1receptor antagonist losartan. In addition, since nitric oxide seems to participate in the mechanism of action of losartan, we studied the effect of the nitric oxide synthesis inhibitor,NG-nitro-L-arginine methyl ester (L-NAME), on the action of losartan.Materials and methodsDose-response curves of either endothelin-1 (10−10to 10−7mol/l) or U46619 (10−10to 10−6mol/l) were studied in the presence or absence of losartan (10-5mol/l) in aortic rings from SHR. Likewise, similar experiments were done in aortic rings pretreated with the nitric oxide synthesis inhibitor, L-NAME (10−4mol/l).ResultsPre-incubation with losartan significantly reduced the contractile response to endothelin-1 compared with control rings, without modifying the value represented by 50% of the maximal response (pD2). The concentration-response curve to U46619 was shifted to the right in the presence of losartan, reducing the pD2compared with control rings. The presence of captopril (10-5mol/l) in the incubation media did not alter the response to either endothelin-1 or U46619. The diminished response to both endothelin-1 and U46619 in the presence of losartan was reversed in L-NAME-pretreated rings.ConclusionsAngiotensin II seems to participate in the vasoconstriction induced by both endothelin-1 and the thromboxane A2analogue through the stimulation of AT1receptors in SHR aortic rings, because losartan inhibited this effect. Moreover, nitric oxide appears to be involved in this action of losartan.
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