Arterial responses to bradykinin after ramipril therapy in experimental hypertension

Pharmacol Toxicol. 1997 Oct;81(4):190-6. doi: 10.1111/j.1600-0773.1997.tb02067.x.

Abstract

Angiotensin-converting enzyme inhibitors have been shown to potentiate relaxations to kinins in several arteries, but the effects of long-term therapy on the responses to bradykinin in normotensive and hypertensive animals remain largely unknown. Therefore, the effects of 12-week-long ramipril therapy (1 mg kg-1 day-1) on responses of mesenteric arterial rings in vitro were studied in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. Endothelium-dependent relaxations of noradrenaline-precontracted rings to acetylcholine were similar in normotensive rats and ramipril-treated hypertensive rats and more pronounced than in untreated hypertensive group. Higher concentrations of bradykinin (0.1-1 microM) induced slight contractions in noradrenaline-precontracted endothelium-intact rings of normotensive groups and untreated hypertensive group, whereas no response or a transient relaxation were observed in ramipril-treated hypertensive rats. Interestingly, in ramipril-treated hypertensive rats but not in the other groups, 20-min. pretreatment of arterial rings with ramiprilat unmasked or potentiated the relaxations to bradykinin, and these bradykinin-induced relaxations were effectively inhibited by the B2-kinin receptor antagonist Hoe-140. In conclusion, ramipril treatment clearly improved endothelium-dependent arterial relaxation to acetylcholine, and potentiated of even unmasked the dilatory response mediated via the endothelial B2-kinin receptor in spontaneously hypertensive rats. Since these enhancing effects on arterial relaxation in vitro could not be attributed to reduced breakdown of bradykinin, the present results suggest that long-term angiotensin-converting enzyme inhibition potentiated the actions of kinins at level of B2-kinin receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Animals
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / drug effects
  • Body Weight / drug effects
  • Bradykinin / metabolism
  • Bradykinin / pharmacology*
  • Disease Models, Animal
  • Endothelium, Vascular / drug effects
  • Heart / drug effects
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Male
  • Mesenteric Arteries / drug effects
  • Muscle Relaxation / drug effects
  • Muscle, Smooth, Vascular / drug effects*
  • Norepinephrine
  • Organ Size / drug effects
  • Ramipril / pharmacology
  • Ramipril / therapeutic use*
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Receptors, Bradykinin / drug effects
  • Receptors, Bradykinin / metabolism
  • Serotonin

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Receptors, Bradykinin
  • Serotonin
  • Ramipril
  • Acetylcholine
  • Bradykinin
  • Norepinephrine