BLOCKADE OF BRADYKININ B-2 RECEPTORS PREVENTS THE INCREASE IN CAPILLARY DENSITY-INDUCED BY CHRONIC ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR TREATMENT IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

We investigated the mechanism of action of the ACE inhibitor-induced i ncrease in cardiac capillary length density. Stroke-prone spontaneousl y hypertensive rats were treated prenatally and up to the age of 20 we eks with the ACE inhibitor ramipril (0.01 and 1 mg/kg per day PO) and the AT1 receptor antagonist losartan (30 mg/kg per day PO). The contri bution of endogenous bradykinin potentiation to the ACE inhibitor acti ons was assessed by cotreatment with the bradykinin B-2-receptor antag onist Icatibant (0.5 mg/kg per day, SC via osmotic minipumps) from 6 t o 20 weeks of age. At the end of the treatment period, cardiac capilla ry length density was measured stereologically using the orientator me thod. The development of hypertension and left ventricular hypertrophy was prevented by high- but not low-dose ramipril and was not affected by chronic bradykinin Bz-receptor blockade. Low- and high-dose ramipr il significantly increased cardiac capillary length density (3577 +/- 279, n = 11 and 3988 +/- 300 mm/mm(3); n = 10; P < .05) compared with vehicle-treated animals (2935 +/- 137 mm/mm(3); n = 13).