title: 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 (AT(1)-) receptors affects reflex control of the circulation and the kidney. In conscious rabbits, the effects of candesartan 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(2) for 30 min) 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 U(Na+)V (-83 ± 10%) fell. AT(1)-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.
authors.affiliation: Department of Physiology, Monash University Melbourne, VIC, Australia.
authors.forename: Tony B
authors.initials: TB
authors.lastname: Xu
authors.forename: Gabriela A
authors.initials: GA
authors.lastname: Eppel
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Head
authors.forename: Roger G
authors.initials: RG
authors.lastname: Evans