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, P < 0.01 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 blockade of angiotensin AT1 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+/+, P < 0.01), as well as by an exaggerated tachycardic response to chronic hypertension induced by clipping of the left renal artery (60 +/- 3 vs. 15 +/- 3 beats/min in B2+/+, P < 0.01). Our findings indicate that disruption of the bradykinin B2-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.
Madeddu
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P
National Laboratory of the National Institute of Biostructures and Biosystems, Osilo, Italy.
Salis
M B
MB
Emanueli
C
C
D000777:Anesthetics; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology; D001340:Autonomic Nerve Block; D017704:Baroreflex / Q000187:drug effects / Q000235:genetics*; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D005730:Ganglionic Blockers / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009539:Nicotinic Acids / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000172:deficiency / Q000235:genetics*; D013777:Tetrazoles / Q000494:pharmacology
D000777:Anesthetics; D057911:Angiotensin Receptor Antagonists; D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D005730:Ganglionic Blockers; D009539:Nicotinic Acids; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D013777:Tetrazoles; C081174:A 81988