Autonomic control in rats with overactivity of tissue renin-angiotensin or kallikrein-kinin system

The renin-angiotensin system (RAS) plays an important role in the regulation of the cardiovascular system and the kallikrein-kinin system (KKS) appears to counteract most of the RAS effects. In this study the vagal and the sympathetic influences on the heart rate and the baroreflex control of the heart rate were evaluated in transgenics rats with human tissue kallikrein gene expression [TGR(hKLK1)], and transgenics rats with tissue renin overexpression [TGR(mREN2)27]. Heart rate was similar in all groups but mean arterial pressure was higher in mREN2 rats than in kallikrein and control rats (149 ± 4 vs. 114 ± 3 vs. 113 ± 3 mm Hg, respectively). The intrinsic heart rate was lower in mREN2 rats than in kallikrein and control rats (324 ± 5 vs. 331 ± 3 vs. 343 ± 7 bpm). The HR response to atropine was similar but the response to propranolol was higher in kallikrein rats than control group (61 ± 7 vs. 60 ± 9 vs. 38 ± 7 bpm, respectively). The vagal tonus was lower in mREN2 than in SD and hKAL rats (18 ± 3 vs. 40 ± 6 vs. 35 ± 6 bpm) whereas the sympathetic tonus was higher in kallikrein rats (118 ± 7 vs. 96 ± 1 vs. 81 ± 9 bpm in the mREN2 and SD rats), respectively. Baroreflex sensitivity to bradycardic responses was attenuated in mREN2 rats (0.37 ± 0.05 vs. 1.34 ± 0.08 vs. 1.34 ± 0,13 bpm/mm Hg) while the tachycardic responses were unchanged. The bradycardic responses to electrical stimulation of the vagal nerve were depressed in both renin and kallikrein rats (129 ± 47 vs. 129 ± 22 vs. 193 ± 25 bpm in control group in response to 32 Hz). In conclusion: 1.The rats with overexpression of renin showed decreased intrinsic heart rate and impairment of vagal function, characterized by decreased vagal tonus, reduced response of HR to electrical stimulation of vagus nerve, and depressed reflex bradycardia provoked by increases of blood pressure. 2. The rats with overexpression of kallikrein showed an increase of sympathetic activity that regulates the heart rate, characterized by increased HR response to propranolol and increased sympathetic tonus, accompanied by decreased bradycardic responses to electrical vagal stimulation.