Altered pulmonary vascular smooth muscle responsiveness in monocrotaline-induced pulmonary hypertension.

Studies were conducted to determine whether experimental pulmonary hypertension is associated with alterations in pulmonary vascular smooth muscle responsiveness. Adult male rats were given a single s.c. injection of monocrotaline (105 mg/kg) or saline and were sacrificed 4, 7 or 14 days later. Segments of the main trunk and right extrapulmonary artery and an intrapulmonary artery were isolated for determination of vascular reactivity to contractile and relaxant agonists. Monocrotaline treatment caused changes in mechanical properties of pulmonary arteries in that vessels isolated from rats 14 days after monocrotaline administration required greater passive loads to achieve maximal active force development. Cumulative concentration-response curves were generated to potassium chloride, angiotensin II, norepinephrine, isoproterenol and acetylcholine. Vascular contractility was enhanced in main pulmonary artery 4 days after monocrotaline injection but no differences in responsiveness between control and monocrotaline exposed vessels were observed 7 days post-treatment. In contrast, significant decreases in contractility with a specific loss in the response to angiotensin II were observed in pulmonary arteries isolated from rats 14 days after monocrotaline administration. These vessels also were less responsive to the relaxant effects of isoproterenol and acetylcholine when compared to control vessels. These results demonstrate that changes in pulmonary vascular smooth muscle responsiveness occur during evolution of pulmonary hypertension induced by monocrotaline. Enhanced contractility may contribute to inappropriate vasoconstriction early in the development of hypertensive pulmonary vascular disease but does not appear to be involved in sustained elevations in pulmonary artery pressure. Diminished relaxation observed after pulmonary hypertension was well established may contribute to the loss in efficacy of vasodilators in the long-term management of pulmonary hypertension.
AuthorsR J Altiere, J W Olson, M N Gillespie
JournalThe Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 236 Issue 2 Pg. 390-5 (Feb 1986) ISSN: 0022-3565 [Print] UNITED STATES
PMID3080584 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Pyrrolizidine Alkaloids
  • Angiotensin II
  • monocrotaline pyrrole
  • Potassium Chloride
  • Monocrotaline
  • Isoproterenol
  • Acetylcholine
  • Norepinephrine
  • Acetylcholine (pharmacology)
  • Angiotensin II (pharmacology)
  • Animals
  • Dose-Response Relationship, Drug
  • Hypertension, Pulmonary (chemically induced, physiopathology)
  • In Vitro Techniques
  • Isoproterenol (pharmacology)
  • Male
  • Monocrotaline
  • Muscle, Smooth, Vascular (drug effects)
  • Norepinephrine (pharmacology)
  • Potassium Chloride (pharmacology)
  • Pulmonary Artery (drug effects)
  • Pyrrolizidine Alkaloids (toxicity)
  • Rats
  • Rats, Inbred Strains
  • Vasoconstriction (drug effects)

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