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 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 (UNa+V) increased fourfold. After vehicle treatment, hypoxia (10% inspired O2 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 UNa+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 UNa+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 UNa+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 AT1-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.

Changes in levels of angiotensin II and its receptors in a model of inverted stress-induced cardiomyopathy

“…It is well established that angiotensin II can stimulate epinephrine release from the adrenal glands [15, 23]. The present study is the first to show that the plasma concentration of angiotensin II increases gradually in SIC.…”

“…Recently, epinephrine-induced cardiotoxicity has been postulated to be involved in the pathogenesis of SIC [ 5 , 22 ]. It is well established that angiotensin II can stimulate epinephrine release from the adrenal glands [ 15 , 23 ]. The present study is the first to show that the plasma concentration of angiotensin II increases gradually in SIC.…”

“…Northern blotting and reverse transcription-polymerase chain reaction (RT-PCR) analyses have been used to identify AT1 and AT2 mRNA in many cells and tissues (including the human myocardium). Pharmacological studies have revealed that the AT1 subtype mediates responses to angiotensin II caused by the release of aldosterone and epinephrine [ 15 ]. One study showed that expression of angiotensin-II receptors changes in response to stress [ 16 ].…”