Abstract 420: Knockout Mice for Elastase-2, a Novel Angiotensin II Generating Enzyme, Displayed Reduced Sympathetic Modulation of Arterial Pressure and Heart Rate

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A functional alternative pathway for angiotensin converting enzyme (ACE) in the generation of angiotensin II was described involving the tissue enzyme elastase-2 (ELA2). This notion was provided by studies from arteries (mesenteric and carotid) and heart of normotensive Wistar rats. The increased mRNA expression of ELA2 associated with chronic ACE inhibition in the carotid artery and heart from spontaneously hypertensive rats (SHR) is remarkable. Quite recently, our group developed the ELA2 knockout (KO) mice. Therefore, the objective of the current study was to examine the cardiovascular profile of ELA2 KO mice. Male ELA2 KO and C57BL/6j wild-type (WT) mice (10-14 weeks; n=6-10) were investigated. Five days after the cannulation of the femoral artery under isoflurane anesthesia, the arterial pressure (AP) and heart rate (HR) were recorded in conscious state. The variability of AP and pulse interval (PI) was examined in the frequency domain using Fast Fourier Transform (FFT) algorithm. AP and PI spectra were integrated in low (LF: 0.25 to 1.0 Hz) and high frequency (HF: 1.0 to 5.0 Hz) bands. The mean AP of WT and KO mice was similar (110 ± 3 vs. 117 ± 5 mmHg in KO). However, decreased HR (512 ± 13 vs. 425 ± 17 bpm) and increased PI (117 ± 5 vs. 142 ± 5 ms) were observed in KO mice. KO mice showed lower LF power (7.2 ± 1.6 vs. 1.3 ± 0.47 mmHg2) in the systolic AP spectrum indicating an attenuation of sympathetic modulation in the AP control. The LF power in the PI spectrum was lower (39 ± 4 vs. 25 ± 3.8 nu) in KO mice. The LF/HF ratio was also reduced in KO mice (0.88 ± 0.16 vs. 0.39 ± 0.07) indicating a shift towards parasympathetic modulation of the HR. In conclusion, KO mice for ELA2 displayed a reduced sympathetic modulation of AP and HR indicating that this enzyme plays a role in the cardiocirculatory control in mice.

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