Abstract 079: (pro)renin Receptor Knockdown In The Paraventricular Nucleus Of Hypothalamus Attenuates The Development Of Doca-salt Hypertension
We previously reported that neuron-specific PRR deletion prevents the development of deoxycorticosterone acetate (DOCA)-salt induced hypertension. However, it is not clear which brain region is responsible for the effect of PRR knockout on the development of hypertension. In present study, we bilaterally micro-injected adeno-associated virus (AAV2)-mediated Cre recombinase with an eGFP tag (AAV-Cre, 50 nl/side) into the paraventricular nucleus of hypothalamus (PVN) of PRR-Floxed mice to knockdown the PRR expression in this region. Deoxycorticosterone acetate-salt (DOCA, 50mg, 0.9%NaCl drinking solution, 21 days) treatment was started 3 days after AAV-Cre or control virus (AAV-eGFP) injection. Blood pressure (BP) was monitored using radio telemetric probes in conscious animals. Autonomic functions were also assessed using pharmacological methods. PVN was micro-punched for PRR real time PCR to verify PRR knockdown efficiency. Three days after virus injection, AAV-Cre significantly decreased PRR expression (fold change: 0.69 ± 0.1 vs. 1.0 ± 0.05) in the PVN compared to AAV-eGFP before DOCA-salt treatment. Three weeks after DOCA-salt treatment, PRR mRNA levels were increased in the AAV-eGFP group (fold change: 3.0 ± 0.1), and this increase was abolished by AAV-Cre (fold change: 1.2 ± 0.04, P<0.05). AAV-Cre expression in the PVN had no effect on PRR expression in the cerebral cortex or brain stem. Blood pressure (mmHg) and heart rate (HR, bpm) were recorded at baseline and following DOCA-salt treatment. AAV-Cre or control virus had no effect on baseline BP or HR. Following DOCA-salt treatment, BP was significantly increased in mice treated with AAV-eGFP (138.5 ± 7.4); while BP was significantly lower in AAV-Cre treated mice (118.9 ± 3.4). The cardiac sympathetic tone (ΔHR to propranolol: -123 ± 46 vs. -181 ± 16) and vasomotor sympathetic tone (ΔBP to chlorisondamine: -47 ± 9.2 vs. -69 ± 4.7) were significantly lower in AAV-Cre treated mice after DOCA-salt treatment. The cardiac parasympathetic tone (ΔHR to methylatropine: 82 ± 18 vs. 40 ± 7.3) was greater in AAV-Cre treated mice. In summary, PRR knockout in the PVN attenuates the development of DOCA-salt hypertension and is associated with the improvement of autonomic function.
Author Disclosures: W. Li: None. Y. Feng: None.
This research has received full or partial funding support from the American Heart Association, National Center.
- © 2014 by American Heart Association, Inc.