AT1 receptors in the paraventricular nucleus mediate the hyperthermia-induced reflex reduction of renal blood flow in rats.
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 = 5) or losartan (1 nmol/100 nl) (n = 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 = 4) or saline (n = 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 (-48 ± 5% from a resting level of 14.3 ± 1.4 ml/min) and MVC (-40 ± 4% from a resting level of 0.128 ± 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.
School of Medical Sciences, Royal Melbourne Institute of Technology University, P.O. Box 71, Bundoora 3083, Melbourne, Victoria, Australia.
Feng
F
Chen
Fang
F
Liu
Emilio
E
Badoer
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000502:physiology; D005334:Fever / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D019808:Losartan / Q000494:pharmacology; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D012018:Reflex / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D012965:Sodium Chloride / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D012965:Sodium Chloride; D019808:Losartan