Cardiovascular responses produced by resistin injected into paraventricular nucleus mediated by the glutamatergic and CRFergic transmissions within rostral ventrolateral medulla

Resistin, as a 12.5 kDa cysteine-rich polypeptide, is expressed in hypothalamus and regulates sympathetic nerve activity. It is associated with obesity, metabolic syndrome and cardiovascular diseases. In this study, we investigated the neural pathway of cardiovascular responses induced by injection of resistin into paraventricular nucleus (PVN) with rostral ventrolateral medulla (RVLM). Adult male rats were anesthetized with urethane (1.4 g/kg intraperitoneally). Resistin (3 µg/1 µl/rat) was first injected into PVN, and the glutamatergic, corticotrophin-releasing factor (CRF)-ergic and angiotensinogenic transmission was inhibited by injecting of their antagonist in RVLM. Arterial pressure (AP) and heart rate (HR) were monitored before and after the injection. The results showed that resistin injection into PVN significantly increased AP and HR compared to control group and prior to its injection (P<0.05). Injection of AP5 ((2R)-amino-5-phosphonovaleric acid; (2R)-amino-5-phosphonopentanoate) (50 nM/rat), losartan (10 nM/rat) and astressin (50 nM/rat) into RVLM reduced cardiovascular responses produced by injected resistin into PVN. Injection of AP5+losartan or astressin+losartan or astressin+AP5 into RVLM could significantly reduce cardiovascular responses produced by resistin compared to before injection (P<0.05). Furthermore, the depressor responses generated by AP5+losartan injected into RVLM were significantly stronger than the depressor responses generated by AP5+astressin and/or astressin+losartan injected into RVLM (P<0.05). It can be concluded that glutamatergic and CRFergic transmissions have crucial contribution to cardiovascular responses produced by resistin. The results provided new and potentially important insight regarding neural transmission when the plasma level of resistin increases; this reveals the role of resistin in cardiovascular responses such as metabolic syndrome and hypertension.