Myocardial and vascular actions of amiloride in spontaneously hypertensive rats.

Experiments were conducted to characterize the cardiovascular actions of the potassium-sparing diuretic amiloride in spontaneously hypertensive and normotensive Wistar-Kyoto rats. Amiloride produced dose-dependent and sustained reductions in blood pressure in spontaneously hypertensive, but not Wistar-Kyoto rats. In intact spontaneously hypertensive rats, amiloride reduced blood pressure, heart rate and myocardial oxygen consumption, and increased simultaneously myocardial contractility. The antihypertensive response was unaltered by bilateral nephrectomy, atropine, cimetidine plus mepyramine, sulpiride and ouabain, but was prevented by phentolamine, hexamethonium and reserpine. Pressor responses to norepinephrine, tyramine, phenylephrine and clonidine were depressed significantly after amiloride, suggesting that amiloride interfered with alpha adrenoceptor-mediated vasoconstriction; vascular reactivity to arginine vasopressin, isoproterenol, histamine and acetylcholine was unaltered. The bradycardic response to amiloride persisted in all groups of animals in spite of surgical or pharmacological pretreatments; positive chronotropic responses to isoproterenol were unaltered by amiloride. The positive inotropic responses to amiloride were evident in the presence of bradycardia, and under conditions in which afterload remained constant or was allowed to decrease. The negative chronotropic and positive inotropic actions of amiloride were due to a direct action of the drug on myocardial tissues, and occurred independently of the antihypertensive effect.

• Publication year

  1986

• Venue

  Journal of Pharmacology and Experimental Therapeutics

• Publication date

  1986-11-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.1016/s0022-3565(25)23601-1PMID 3772800
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Amiloride produced persistent bradycardic responses and increased myocardial contractility while reducing myocardial oxygen consumption in intact spontaneously hypertensive rats.

  Confidence 0.95

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review
• Amiloride depressed pressor responses to norepinephrine, tyramine, phenylephrine, and clonidine, indicating interference with alpha adrenoceptor-mediated vasoconstriction.

  Confidence 0.96

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review
• The antihypertensive response to amiloride was prevented by phentolamine, hexamethonium, and reserpine, but was unaltered by bilateral nephrectomy, atropine, cimetidine plus mepyramine, sulpiride, or ouabain.

  Confidence 0.97

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review
• Amiloride produced dose-dependent, sustained blood pressure reductions in spontaneously hypertensive rats but not in Wistar-Kyoto rats.

  Confidence 0.98

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review

• alpha adrenoceptor-mediated vasoconstriction

  mechanism

  Vascular constriction mediated by alpha adrenergic receptors, assessed through pressor responses in the study.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review
• amiloride

  drug

  The potassium-sparing diuretic tested for cardiovascular effects in the rat experiments.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review
• antihypertensive response

  outcome

  The blood-pressure-lowering response measured after amiloride administration in the animals.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review
• bradycardic response

  outcome

  A slowing of heart rate observed after amiloride exposure.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review
• hexamethonium

  drug

  A ganglionic blocker used as a pretreatment to probe the mechanism of the amiloride response.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review
• myocardial contractility

  physiological process

  The force-generating function of cardiac muscle measured as an inotropic effect in the experiments.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review
• myocardial oxygen consumption

  outcome, measurement

  The amount of oxygen used by the heart muscle as a cardiac metabolic measure in the experiments.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review
• phentolamine

  drug

  An alpha-adrenergic antagonist used as a pharmacological pretreatment in the experiments.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review
• reserpine

  drug

  A catecholamine-depleting drug used as a pretreatment in the cardiovascular tests.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review
• spontaneously hypertensive rats

  animal model

  A rat strain with naturally elevated blood pressure used as the hypertensive experimental model.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review
• wistar-kyoto rats

  animal model

  A normotensive rat strain used as the control comparison group.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewB (s683577b42) reviewmexicorea (qjvnbu8xg3) review

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