AT₁ receptors in the paraventricular nucleus mediate the hyperthermia-induced reflex reduction of renal blood flow in rats

Abstract

Increasing body core temperature reflexly decreases renal blood flow (RBF), and the hypothalamic paraventricular nucleus (PVN) plays an essential role in this response. ANG II in the brain is involved in the cardiovascular responses to hyperthermia, and ANG II receptors are highly concentrated in the PVN. The present study investigated whether ANG II in the PVN contributes to the cardiovascular responses elicited by hyperthermia. Rats anesthetized with urethane (1-1.4 g/kg iv) were microinjected bilaterally into the PVN (100 nl/side) with saline (n ϭ 5) or losartan (1 nmol/100 nl) (n ϭ 7), an AT1 receptor antagonist. Body core temperature was then elevated from 37°C to 41°C and blood pressure (BP), heart rate (HR), RBF, and renal vascular conductance (RVC) were monitored. In separate groups losartan (n ϭ 4) or saline (n ϭ 4) was microinjected into the PVN, but body core temperature was not elevated. Increasing body core temperature in control rats elicited significant decreases in RBF (Ϫ48 Ϯ 5% from a resting level of 14.3 Ϯ 1.4 ml/min) and MVC (Ϫ40 Ϯ 4% from a resting level of 0.128 Ϯ 0.013 ml/min·mmHg), and these effects were entirely prevented by pretreatment with losartan. In rats in which body core temperature was not altered, losartan microinjected into the PVN had no significant effects on these variables. The results suggest that endogenous ANG II acts on AT1 receptors in the PVN to mediate the reduction in RBF induced by hyperthermia.hypothalamus; body temperature; brain; angiotensin ii THERMOREGULATION IS A VITAL, fundamental physiological function that enables the body to defend itself from external and internal temperature changes. There are a number of cardiovascular mechanisms that help do this; for example, during hyperthermia in humans, blood flow is redirected from the viscera (e.g., renal and splanchnic regions) to the skin so that the body may dissipate heat. Such responses are brought about by altering sympathetic nerve activity. Increasing sympathetic nerve activity to the vasculature of visceral organs like the kidneys and mesentery is important since failure to adequately vasoconstrict these in response to hyperthermia can cause a dramatic reduction in cardiac output and the resultant lifethreatening sequelae of heat stroke (22-23).The hypothalamus, in particular, plays a key role in thermoregulation and the hypothalamic paraventricular nucleus (PVN), located adjacent to the third ventricle in the forebrain, is an important integrative site involved in hormonal, endocrine, and peripheral neural control.Activation of the PVN can cause a pronounced alteration in blood pressure, sympathetic neural outflows, and hemodynamic responses (5-6, 11, 21, 31). There are several lines of evidence supporting a role of the PVN in the cardiovascular responses elicited during thermoregulation: 1) the PVN contains neurons that project to areas important for thermoregulation, such as the brown adipose tissue, the tail (in the rat), kidney, and gut (19, 26, 30, 34 -35); 2) the PVN can influence sympathetic ne...

The central renin–angiotensin system and sympathetic nerve activity in chronic heart failure

“…Areas in the rostral ventrolateral medulla (RVLM) and in the hypothalamus, (e.g. the paraventricular nucleus (PVN)) have been shown to mediate an increase in sympathetic outflow in response to microinjection of Ang II [15][16][17][18][19][20][21][22][23][24][25]. In studies carried out in rabbits with pacing-induced CHF Liu et al [26] showed that central infusion of the AT1R blocker losartan reduced renal sympathetic nerve activity (RSNA).…”

Organs Blood Flow during Elevation of Body Temperature in Sevoflurane Anesthetized Rats

“…Nitric oxide and angiotensin II (acts on angiotensin 1A receptor) in the PVN are important in mediating the decrease of mesenteric and renal blood flow during hyperthermia [11, 12]. Sevoflurane does not affect the angiotensin 1A receptor signaling [13].…”

“…The hypothalamic paraventricular nucleus (PVN) seems to play a key role for decrease of the mesenteric and renal blood flow during hyperthermia [ 9 , 10 ]. Nitric oxide and angiotensin II (acts on angiotensin 1A receptor) in the PVN are important in mediating the decrease of mesenteric and renal blood flow during hyperthermia [ 11 , 12 ]. Sevoflurane does not affect the angiotensin 1A receptor signaling [ 13 ].…”

Hypothalamic GPCR Signaling Pathways in Cardiometabolic Control

“…Early studies found that AT1a is critical for the BP response effects of the brain RAS, whereas the AT1b receptor is involved in the dipsogenic effects of central ANG actions ( Davisson et al, 2000 ). Blockade of AT1a and AT1b receptors with the antagonist losartan in the paraventricular nucleus (PVN) prevents the reflex reduction in renal blood flow induced by elevated core body temperature, underscoring this receptor as a critical mediator of cardiovascular thermoregulatory responses ( Chen et al, 2011 ).…”