Kinins and the events influenced by an angiotensin-converting enzyme inhibitor during neointima formation in the rat carotid artery.

Objective: In balloon-injured rat carotid arteries, angiotensin-converting enzyme inhibitors (ACEI) decrease neointima formation, and a kinin receptor antagonist partially reverses this inhibitory effect. We studied which of the events leading to neointima formation are involved in the effects of ACEI and kinins.

Methods: We administered 5 mg/kg per day ramipril, either alone or combined with the kinin receptor antagonist icatibant (Hoe 140), on the days each wave occurred and studied the effects on neointima formation 14 days after balloon injury.

Role of kinins and nitric oxide in the effects of angiotensin converting enzyme inhibitors on neointima formation.

Marked neointima formation occurs after balloon injury to the intima of rat arteries. Angiotensin II has been implicated as a growth factor in this process, since angiotensin converting enzyme (ACE) inhibitors block neointima formation after injury. However, ACE is an important kininase, and its inhibitors may act in part by a kinin-mediated mechanism.

Endothelium-derived relaxing factor inhibits transport and increases cGMP content in cultured mouse cortical collecting duct cells.

Stimulation of the release of endothelium-derived relaxing factor (EDRF) in the kidney has been shown to result in natriuresis without affecting glomerular filtration rate. This may be due to EDRF directly regulating solute transport in the cortical collecting duct (CCD). To test this hypothesis, we measured the effect of bradykinin (Bk) or acetylcholine (Ach) on short-circuit current (Isc; a measure of active transport) in a CCD cell line (M-1), in the presence or absence of cow pulmonary artery endothelial (CPAE) cells.

Kinins mediate the antiproliferative effect of ramipril in rat carotid artery.

Angiotensin-converting enzyme (ACE) inhibitors have been shown to inhibit neointimal proliferation in response to endothelial injury in the rat carotid artery. Since ACE inhibitors block degradation of kinins, our objective in this study was to determine whether kinins mediate the antiproliferative effect of the ACE inhibitor ramipril. Endothelial denudation was achieved in the left carotid artery of male Sprague-Dawley rats using a balloon catheter.