Intravenous vasopressin leads to greater haemodynamic and respiratory responses in spontaneously hypertensive SHR rats than in normotensive controls

Abstract

Introduction Increased activity of vasopressinergic system has been implicated in pathophysiology of essential hypertension. Intravenous or central administrations of vasopressin (AVP) were shown to affect not only hemodynamics, but also ventilatory function in rats. Receptors for AVP have been found in the brainstem structures involved in the control of breathing and in the carotid bodies. We hypothesized that given the involvement of AVP in essential hypertension and control of ventilation, AVP may differently affect hemodynamics and ventilation in spontaneously hypertensive (SHR) and in normotensive Wistar-Kyoto (WKY) rats. Purpose In the study we investigated the effects of intravenously administered AVP on hemodynamic and respiratory parameters under hypertensive and normotensive conditions. Methods The study was performed in urethane-anesthetizes adult male normotensive WKY (n=7) and hypertensive SHR rats (n=7). We implanted catheters into the femoral artery and femoral vein for recording mean arterial blood pressure (MABP) and for intravenous infusions, respectively. Additionally, we recorded minute ventilation (MV), respiratory rate (RR) and end-tidal CO2 (ET-CO2) via tracheal tube. We also placed subcutaneous ECG electrodes for heart rate (HR) monitoring. After obtaining baseline parameters, the arterial chemoreflex was triggered pharmacologically with intravenous (i.v.) administration of potassium cyanide (KCN) (30 microg/100 microL). After stabilization of hemodynamic and respiratory parameters, rats received i.v. administration of AVP (10ng/100μL) and recordings continued. Results SHR rats had significantly higher resting MABP, HR and MV than WKY controls. Both increases in MABP and MV and decrease in ET-CO2 were significantly greater in SHR than in WKY rats in response to pharmacologically triggered peripheral chemoreflex. One minute after administration of KCN, MV remained elevated above baseline and ET-CO2 was below baseline in SHR rats, whereas all respiratory parameters were normal in WKY rats. In SHR rats administration of AVP resulted in significantly greater increase in MABP than in WKY controls and was accompanied by reduction in MV and RR but no changes in HR. In WKY rats AVP resulted in smaller MABP increase accompanied by insignificant changes in respiratory parameters or HR. Conclusions Our findings confirm increased sensitivity of arterial chemoreflex in urethane-anesthetized SHR rats and suggest that AVP-dependent pressor and respiratory responses are enhanced in spontaneously hypertensive rats.