Altered baroreflex control of heart rate in bradykinin B-2-receptor knockout mice

Recently, we have shown that a knockout mouse strain lacking the bradykinin B-2-receptor gene exhibits an accelerated heart rate (HR) under basal cond itions, this alteration being associated with mildly elevated blood pressur e (BP) levels and ultimately with the development of cardiomyopathy. The go al of the present study was to determine whether genetic disruption of the B-2-receptor alters autonomic cardiovascular reflexes to acute or chronic c hanges in BP. The direct mean BP and HR levels of unrestrained B-2 knockout mice (B-2(-/-)) were higher than those of wild type (B-2(+/+)) controls (1 31 +/- 2 vs. 105 +/- 2 mm Hg and 480 +/- 5 vs. 414 +/- 8 beats/min, P < 0.0 1 for both comparisons). The difference in HR observed between groups under basal conditions was nullified by the acute administration of propranolol and atropine as well as by hexamethonium; it was attenuated by long-term bl ockade of angiotensin AT(1) receptors. In B-2(-/-) mice, the presence of an alteration in baroreceptor regulation of HR was supported by a reduced gai n in the HR responses to acute nitroprusside-induced hypotension or phenyle phrine-induced hypertension (slope of the regression line: 0.82 +/- 0.07 vs . 5.58 +/- 0.08 beats/min per mmHg in B-2(+/+), P < 0.01), as well as by an exaggerated tachycardic response to chronic hypertension induced by clippi ng of the left renal artery (60 +/- 3 vs. 15 +/- 3 beats/min in B-2(+/+), P < 0.01). Our findings indicate that disruption of the bradykinin B-2-recep tor gene is associated with an impaired baroreflex control of HR. The combi nation of chronically elevated resting HR and impaired baroreflex. control could contribute to the development of cardiomyopathy in these animals. (C) 1999 Elsevier Science B.V. All rights reserved.