Influence of PLC and MLCK inhibitors and the role of L-calcium channels in the cat pulmonary vascular bed

Am J Physiol. 1995 Oct;269(4 Pt 1):L507-13. doi: 10.1152/ajplung.1995.269.4.L507.

Abstract

The effects of U-73122, a phospholipase C (PLC) inhibitor, on pressor responses to angiotensin II (ANG II), norepinephrine (NE), serotonin (5-HT), BAY K 8644, and the thromboxane A2 (TxA2) mimic, U-46619, were studied in the pulmonary vascular bed of the intact-chest cat. Under conditions of constant lobar blood flow, injections of ANG II, NE, 5-HT, U-46619, and the calcium channel opener, BAY K 8644, into the lobar arterial perfusion circuit caused dose-related increases in lobar arterial pressure, which were reproducible with respect to time. Infusion of U-73122, a PLC inhibitor, into the perfused lobar artery at 10-100 micrograms/kg for 10 min significantly reduced responses to ANG II, serotonin, and NE; however, U-73122 did not alter responses to BAY K 8644 or to U-46619. In a separate series of animals, the effects of the myosin light chain kinase inhibitor, KT-5926, were investigated, and after infusion of KT-5926 into the perfused lobar artery at 1-2 micrograms/kg for 10 min, responses to ANG II, NE, 5-HT, BAY K 8644, and U-46619 were reduced significantly. In a final series of experiments, the effects of the L-type calcium channel blocker, nicardipine, were investigated, and infusion of the L-type calcium channel blocker into the perfused lobar artery at 0.5-1 microgram/kg for 10 min reduced responses to ANG II, BAY K 8644, and NE. However, nicardipine did not alter pressor responses to 5-HT or the TxA2 mimic, U-46619.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Alkaloids / pharmacology
  • Animals
  • Blood Vessels / drug effects
  • Blood Vessels / physiology
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / physiology*
  • Carbazoles*
  • Cats
  • Estrenes / pharmacology
  • Female
  • Indoles*
  • Male
  • Myosin-Light-Chain Kinase / antagonists & inhibitors*
  • Nicardipine / pharmacology
  • Pulmonary Circulation* / drug effects
  • Pyrrolidinones / pharmacology
  • Type C Phospholipases / antagonists & inhibitors*
  • Vasoconstrictor Agents / pharmacology

Substances

  • Alkaloids
  • Calcium Channel Blockers
  • Calcium Channels
  • Carbazoles
  • Estrenes
  • Indoles
  • Pyrrolidinones
  • Vasoconstrictor Agents
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • KT 5926
  • Nicardipine
  • Myosin-Light-Chain Kinase
  • Type C Phospholipases