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...