| Losartan but not verapamil inhibits angiotensin II-induced tissue endothelin-1 increase: role of blood pressure and endothelial function. | |
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MedLine Citation:
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PMID: 9622146 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Endothelin partially mediates angiotensin (Ang) II-induced vascular changes in vivo. This study investigated the effects of the angiotensin type 1 receptor antagonist losartan and the calcium channel blocker verapamil on vascular reactivity and tissue endothelin-1 levels in aortas of Wistar-Kyoto rats treated for 2 weeks with Ang II (200 ng x kg(-1) x min(-1)). Ang II increased systolic blood pressure (39+/-4 mm Hg, P<0.05). Concomitant treatment with losartan abolished the Ang II-induced pressure increase (P<0.05), whereas verapamil reduced it only partially (P<0.05). In the aortas of rats with Ang II-induced hypertension, tissue endothelin-1 content was increased threefold and contractions to endothelin-1 were impaired (P<0.05). Interestingly, these alterations were normalized by losartan (P<0.05) but not by verapamil. Hence, there was a strong, negative correlation between contractions to endothelin-1 and tissue endothelin-1 content (r=-0.733, P<0.0001). In contrast, both antihypertensive drugs normalized impaired endothelium-dependent relaxations to acetylcholine and reduced the sensitivity of vascular smooth muscle to sodium nitroprusside compared with Ang II-treated rats (P<0.05). Ang II-induced hypertension enhanced endothelium-dependent contractions to acetylcholine, and these were normalized by either drug. In conclusion, these findings suggest that long-term treatment with Ang II modulates endothelin-1 protein expression in the rat aorta. Although both antihypertensive agents lowered blood pressure and normalized endothelial function, only losartan prevented the increase in tissue endothelin-1 content, suggesting that angiotensin type 1 receptor antagonists but not calcium antagonists modulate tissue endothelin-1 in vivo. |
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Authors:
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L V d'Uscio; S Shaw; M Barton; T F Lüscher |
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Publication Detail:
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Type: Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Hypertension Volume: 31 ISSN: 0194-911X ISO Abbreviation: Hypertension Publication Date: 1998 Jun |
Date Detail:
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Created Date: 1998-06-19 Completed Date: 1998-06-19 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1305-10 Citation Subset: IM |
Affiliation:
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Cardiovascular Research, Institute of Physiology, University of Zürich, University Hospital, Zürich, Switzerland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin II Animals Antihypertensive Agents / pharmacology* Aorta, Thoracic / chemistry, drug effects Blood Pressure / physiology Calcium Channel Blockers / pharmacology* Data Interpretation, Statistical Endothelin-1 / analysis, physiology* Endothelium, Vascular / drug effects, physiology* Hypertension / chemically induced, physiopathology* Losartan / pharmacology* Male Muscle, Smooth, Vascular / chemistry, drug effects Nitroprusside / pharmacology Rats Rats, Inbred WKY Receptors, Endothelin / antagonists & inhibitors, drug effects Time Factors Vasoconstriction / drug effects, physiology Vasodilation / drug effects, physiology Vasodilator Agents / pharmacology Verapamil / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Antihypertensive Agents; 0/Calcium Channel Blockers; 0/Endothelin-1; 0/Receptors, Endothelin; 0/Vasodilator Agents; 11128-99-7/Angiotensin II; 114798-26-4/Losartan; 15078-28-1/Nitroprusside; 52-53-9/Verapamil |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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