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PMID: 10821779 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Tissue angiotensin II and endothelin-1 modulate differently the response to flow in mesenteric resistance arteries of normotensive and spontaneously hypertensive rats.

British journal of pharmacology ·Vol. 130 ·No. 3 ·2000-06-00 ·Pages 521-6

Matrougui K, Lévy BI, Henrion D

Abstract

In resistance arteries pressure-induced (myogenic) tone (MT) and flow (shear stress)-induced dilation (FD) are potent determinant of vascular resistance. We investigated the role of angiotensin II and endothelin-1 in FD and MT in resistance arteries and their potential change in hypertension. Flow - diameter - pressure relationship was established in situ, under anaesthesia, in two daughter branches of a mesenteric resistance artery (180 microM, n=7 per group) from spontaneously hypertensive (SHR) or normotensive (WKY) rats. One artery was ligated distally, so that it was submitted to pressure only, while the other was submitted to pressure and flow. Drugs were added to the preparation and external diameter, pressure and flow measured continuously. External diameter (with flow) ranged from 150+/-3 to 191+/-7 microM in WKY (n=28) rats and from 168+/-6 to 186+/-6 microM in SHR (n=28). Flow induced a dilation of the non-ligated arteries which was lower in SHR (13+/-5 - 31+/-4 microM vs WKY: 5+/-5 - 44+/-4 microM). In the ligated artery, the diameter did not significantly change, due to MT. In the vessels submitted to flow angiotensin converting enzyme inhibition (perindopril, 10 micromol L(-1)) increased the diameter in SHR (+11+/-2 microM) significantly more than in WKY (+2+/-1 microM). Angiotensin type 1 receptor (AT(1)R) blockade (losartan, 10 micromol L(-1)) increased the diameter in the vessels with flow in SHR only (+6+/-1 microM). Angiotensin type 2 receptor (AT(2)R) blockade (PD 123319, 1 micromol L(-1)) decreased arterial diameter in WKY only (9+/-2). Endothelin-1 type A receptor (ET(A)R) blockade (LU135252, 0.1 micromol L(-1)) increased the diameter only in SHR in the artery submitted to flow (by 6+/-1 microM). Thus FD was counteracted by a flow-dependent AT(1) and ET(A) receptors-activation in SHR whereas in WKY FD AT(2)-dependent dilation is involved.

MeSH Terms

Angiotensin II/physiology Angiotensin Receptor Antagonists Angiotensin-Converting Enzyme Inhibitors/pharmacology Animals Antihypertensive Agents/pharmacology Blood Viscosity/drug effects,physiology Endothelin Receptor Antagonists Endothelin-1/physiology Hypertension/genetics,physiopathology Imidazoles/pharmacology Losartan/pharmacology Mesenteric Arteries/drug effects,physiology,physiopathology Muscle Tonus/drug effects,physiology Perindopril/pharmacology Phenylpropionates/pharmacology Pyridines/pharmacology Pyrimidines/pharmacology Rats Rats, Inbred SHR Rats, Inbred WKY Receptors, Angiotensin/agonists Splanchnic Circulation/drug effects,physiology Vascular Resistance/drug effects Vasodilation/drug effects,physiology

Chemicals

Angiotensin Receptor Antagonists Angiotensin-Converting Enzyme Inhibitors Antihypertensive Agents Endothelin Receptor Antagonists Endothelin-1 Imidazoles Phenylpropionates Pyridines Pyrimidines Receptors, Angiotensin Angiotensin II PD 123319 darusentan Losartan Perindopril

Authors & Affiliations

3 authors, click to expand affiliations / ORCID

Matrougui K

Institut National de la Santé et de la Recherche Médicale (INSERM) U 541, IFR 6, Université Paris VII, 41 Bd de la Chapelle, 75475 Paris, cedex 10, France.

Lévy B I

Henrion D

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35 references, click to expand

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Article Info

Journal

British journal of pharmacology

Abbr.

Br J Pharmacol

ISSN

0007-1188

DOI

10.1038/sj.bjp.0703371

Published

2000-06-00

Pages

521-6

Language

English

Region

England

NLM ID

7502536

PMCID

PMC1572118

Subset

External Links

PubMed source DOI: 10.1038/sj.bjp.0703371 PMC Full Text View journal details

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Tissue angiotensin II and endothelin-1 modulate differently the response to flow in mesenteric resistance arteries of normotensive and spontaneously hypertensive rats.

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