Angiotensin II type 1 receptors and systemic hemodynamic and renal responses to stress and altered blood volume in conscious rabbits

Abstract

We examined how systemic blockade of type 1 angiotensin (AT1-) receptors affects reflex control of the circulation and the kidney. In conscious rabbits, the effects of candesar-tan on responses of systemic and renal hemodynamics and renal excretory function to acute hypoxia, mild hemorrhage, and plasma volume expansion were tested. Candesartan reduced resting mean arterial pressure (MAP-8±2%) without significantly altering cardiac output (CO), increased renal blood flow (RBF,+38±9%) and reduced renal vascular resistance (RVR, -32±6%). Glomerular filtration rate (GFR) was not significantly altered but sodium excretion (U Na+V) increased fourfold. After vehicle treatment, hypoxia (10% inspired O 2for 30min) did not significantly alter MAP or CO, but reduced heart rate (HR, -17±6%), increased RVR (+33±16%) and reduced GFR (-46±16%) and U Na+V (-41 ± 17%). Candesartan did not significantly alter these responses. After vehicle treatment, plasma volume expansion increased CO (+35±7%), reduced total peripheral resistance (TPR, -26±5%), increased RBF (+62± 23%) and reduced RVR (-32±9%), but did not significantly alter MAP or HR. It also increased U Na+V (803±184%) yet reduced GFR (-47±9%). Candesartan did not significantly alter these responses. After vehicle treatment, mild hemorrhage did not significantly alter MAP but increased HR (+16±3%), reduced CO (-16 ± 4%) and RBF (-18 ±6%), increased TPR (+18 ± 4%) and tended to increase RVR (+18 ± 9%, P =0.1), but had little effect on GFR or U Na+V. But after candesartan treatment MAP fell during hemorrhage (-19± 1%), while neither TPR nor RVR increased, and GFR (-64±18%) and UNa+V(-83±10%) fell. AT1 -receptor activation supports MAP and GFR during hypovolemia. But AT 1-receptors appear to play little role in the renal vasoconstriction, hypofiltration, and antinatriuresis accompanying hypoxia, or the systemic and renal vasodilatation and natriuresis accompanying plasma volume expansion. © 2011 Xu, Eppel, Head and Evans.