Pinacidil-induced relaxation in pulmonary arteries isolated from pulmonary hypertensive and normotensive rats and pre-contracted with different spasmogens

Wanstall J.C., Kay C.S. and O'Donnell S.R. (1994) Pinacidil-induced relaxation in pulmonary arteries isolated from pulmonary hypertensive and normotensive rats and pre-contracted with different spasmogens. Pulmonary Pharmacology, 7 6: 401-408. doi:10.1006/pulp.1994.1047


Author Wanstall J.C.
Kay C.S.
O'Donnell S.R.
Title Pinacidil-induced relaxation in pulmonary arteries isolated from pulmonary hypertensive and normotensive rats and pre-contracted with different spasmogens
Journal name Pulmonary Pharmacology   Check publisher's open access policy
ISSN 0952-0600
Publication date 1994-01-01
Sub-type Article (original research)
DOI 10.1006/pulp.1994.1047
Open Access Status Not yet assessed
Volume 7
Issue 6
Start page 401
End page 408
Total pages 8
Language eng
Subject 2736 Pharmacology (medical)
2740 Pulmonary and Respiratory Medicine
3000 Pharmacology, Toxicology and Pharmaceutics
Abstract Vasorelaxant responses to the potassium channel opening drug, pinacidil, were obtained on preparations of pulmonary artery and aorta taken from rats with pulmonary hypertension (induced by chronic hypoxia or monocrotaline) and pre-contracted either submaximally with endothelin-1 (ET-1), PGF(2α), U466P9 (thromboxane-mimetic) or noradrenaline (NA), or with 80mM K. In pulmonary artery, but not aorta, from pulmonary hypertensive rats the maximum relaxant response to pinacidil was increased, when compared with data in control rats, irrespective of the spasmogen used to precontract the tissues. The increase in maximum was associated with relaxation to below the tissue resting baseline and probably reflected the presence of inherent contractile tone in arteries from pulmonary hypertensive rats. In addition the potency (-log EC) of pinacidil was increased in pulmonary arteries from pulmonary hypertensive rats but this was seen only in preparations contracted with ET-1 (30-fold increase) or NA (seven-fold increase) and not in those contracted with PGF(2α), U46619 or K. As a result, in ET-1-contracter preparations from pulmonary hypertensive rats pinacidil was 29-fold more potent on pulmonary artery than on aorta. To explain the increase in potency it is speculated that during the development of pulmonary hypertension the mechanism whereby ET-1 and NA contract pulmonary arteries may change from one in which Ca influx plays only a minor role to one in which Ca influx predominates, although no direct evidence to support this speculation has yet been obtained.
Keyword Endothelin
Pinacidil
Pulmonary artery
Pulmonary hypertension
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Scopus Import - Archived
 
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