KRN2391: Dual action on rat pulmonary artery and no loss of potency in pulmonary hypertension

Wanstall, Janet C., Gambino, Agatha and Thomas, Bronwyn J. (2000) KRN2391: Dual action on rat pulmonary artery and no loss of potency in pulmonary hypertension. Clinical and Expermental Pharmacology and Physiology, 27 4: 288-294. doi:10.1046/j.1440-1681.2000.03237.x

Author Wanstall, Janet C.
Gambino, Agatha
Thomas, Bronwyn J.
Title KRN2391: Dual action on rat pulmonary artery and no loss of potency in pulmonary hypertension
Journal name Clinical and Expermental Pharmacology and Physiology   Check publisher's open access policy
ISSN 0305-1870
Publication date 2000-04
Sub-type Article (original research)
DOI 10.1046/j.1440-1681.2000.03237.x
Volume 27
Issue 4
Start page 288
End page 294
Total pages 7
Editor Warwick P. Anderson
Place of publication Oxford, U.K.
Publisher Blackwell Science Asia
Collection year 2000
Language eng
Subject C1
320502 Basic Pharmacology
730106 Cardiovascular system and diseases
Formatted abstract
   1. The pulmonary vasorelaxant properties of KRN2391 (N-cyano-N′-(2-nitroxyethyl)-3-pyridinecarboximidamide) were examined in isolated ring preparations of main (MPA) and intralobar (IPA) pulmonary artery from control and pulmonary hypertensive rats (exposure to hypoxia, 10% oxygen, for 1 week).
   2. On both MPA and IPA, pulmonary vasorelaxant responses were inhibited by methylene blue (10 μmol/L) or glibenclamide (1 or 10 μmol/L). Thus, KRN2391 has the properties of both a nitric oxide (NO) donor and a KATP channel opener on rat pulmonary arteries.
   3. KRN2391 was more potent and gave a greater maximum relaxation on MPA (–log EC50 6.47; maximum 92% reversal of induced contraction) than on IPA (–log EC50 6.09; maximum 58% reversal of induced contraction). Comparable differences between MPA and IPA were seen for SIN-1 (NO donor) and levcromakalim (KATP channel opener).
   4. KRN2391 was equipotent in MPA from control and pulmonary hypertensive rats but, when glibenclamide (10 μmol/L) was present, KRN2391 was six-fold less potent in preparations from pulmonary hypertensive than control rats. An eight-fold reduction in potency was seen for SIN-1 (no glibenclamide) in arteries from pulmonary hypertensive rats, confirming previous findings with other NO donors.
   5. It is concluded that the dual mechanism of action of KRN2391 accounts for the finding that this drug is equally potent in pulmonary arteries from pulmonary hypertensive and control rats. In the context of pulmonary hypertension, this property of the drug could give it an advantage over drugs that act solely as NO donors because these decline in potency, at least in animal models of this disease.
Keyword Pharmacology & Pharmacy
Nitric Oxide Donor
Potassium Channel Opener
Pulmonary Artery
Pulmonary Hypertension
Nitric-oxide Donor
Vasodilator Properties
Guanylyl Cyclase
Different Sizes
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 2 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 10 Jun 2008, 11:29:38 EST