Brain-targeted (pro)renin receptor knockdown using short-hairpin RNA significantly reduced blood pressure and sympathetic tone in human renin-angiotensinogen double-transgenic hypertensive mice.
Does intracerebroventricular delivery of adeno-associated virus-mediated (pro)renin receptor short hairpin RNA reduce blood pressure in human renin-angiotensinogen double-transgenic hypertensive mice?
Brain-targeted (pro)renin receptor knockdown attenuates angiotensin II-dependent hypertension in a transgenic mouse model, suggesting a central role for this receptor in hypertension pathogenesis.
The (pro)renin receptor is a newly discovered member of the brain renin-angiotensin system. To investigate the role of brain (pro)renin receptor in hypertension, adeno-associated virus-mediated (pro)renin receptor short hairpin RNA was used to knockdown (pro)renin receptor expression in the brain of nontransgenic normotensive and human renin-angiotensinogen double-transgenic hypertensive mice. Blood pressure was monitored using implanted telemetric probes in conscious animals. Real-time PCR and immunostaining were performed to determine (pro)renin receptor, angiotensin II type 1 receptor, and vasopressin mRNA levels. Plasma vasopressin levels were determined by ELISA. Double-transgenic mice exhibited higher blood pressure, elevated cardiac and vascular sympathetic tone, and impaired spontaneous baroreflex sensitivity. Intracerebroventricular delivery of (pro)renin receptor short-hairpin RNA significantly reduced blood pressure, cardiac and vasomotor sympathetic tone, and improved baroreflex sensitivity compared with the control virus treatment in double-transgenic mice. (Pro)renin receptor knockdown significantly reduced angiotensin II type 1 receptor and vasopressin levels in double-transgenic mice. These data indicate that (pro)renin receptor knockdown in the brain attenuates angiotensin II-dependent hypertension and is associated with a decrease in sympathetic tone and an improvement of the baroreflex sensitivity. In addition, brain-targeted (pro)renin receptor knockdown is associated with downregulation of angiotensin II type 1 receptor and vasopressin levels. We conclude that central (pro)renin receptor contributes to the pathogenesis of hypertension in human renin-angiotensinogen transgenic mice.
Li et al. (Tue,) conducted a other in Angiotensin II-dependent hypertension. Adeno-associated virus-mediated (pro)renin receptor short hairpin RNA vs. Control virus treatment was evaluated on Blood pressure, cardiac and vasomotor sympathetic tone, and baroreflex sensitivity. Brain-targeted (pro)renin receptor knockdown using short-hairpin RNA significantly reduced blood pressure and sympathetic tone in human renin-angiotensinogen double-transgenic hypertensive mice.
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