Altered baroreflex control of heart rate in bradykinin B2-receptor knockout mice

Recently, we have shown that a knockout mouse strain lacking the bradykinin B₂-receptor gene exhibits an accelerated heart rate (HR) under basal conditions, this alteration being associated with mildly elevated blood pressure (BP) levels and ultimately with the development of cardiomyopathy. The goal of the present study was to determine whether genetic disruption of the B₂-receptor alters autonomic cardiovascular reflexes to acute or chronic changes in BP. The direct mean BP and HR levels of unrestrained B₂ knockout mice (B₂(-/-)) were higher than those of wild type (B₂(+/+)) controls (131±2 vs. 105±2 mm Hg and 480±5 vs. 414±8 beats/min, P1 receptors. In B₂(-/-) mice, the presence of an alteration in baroreceptor regulation of HR was supported by a reduced gain in the HR responses to acute nitroprusside-induced hypotension or phenylephrine-induced hypertension (slope of the regression line: 0.82±0.07 vs. 5.58±0.08 beats/min per mmHg in B₂(+/+), P2(+/+), P2-receptor gene is associated with an impaired baroreflex control of HR. The combination of chronically elevated resting HR and impaired baroreflex control could contribute to the development of cardiomyopathy in these animals. Copyright (C) 1999 Elsevier Science B.V.