Role of the hypothalamic PVN in the reflex reduction in mesenteric blood flow elicited by hyperthermia

Abstract

In the present study, we investigated whether the PVN is a key region in the mesenteric vasoconstriction that normally accompanies an increase in core body temperature. Anesthetized rats were monitored for blood pressure, heart rate, mesenteric blood flow, and vascular conductance. In control rats, elevation of core body temperature to 41°C had no significant effect on blood pressure, increased heart rate, and reduced mesenteric blood flow by 21%. In a separate group of rats, muscimol was microinjected bilaterally (1 nmol/side) into the PVN. Compared with the control group, there was no significant difference in the blood pressure and heart rate responses elicited by the increase in core body temperature. In contrast to control animals, however, mesenteric blood flow did not fall in the muscimol-treated rats in response to the elevation in core body temperature. In a separate group, in which muscimol was microinjected into regions outside the PVN, elevating core body temperature elicited the normal reduction in mesenteric blood flow. The results suggest that the PVN may play a key role in the reflex decrease in mesenteric blood flow elicited by hyperthermia.reflex mesenteric blood flow; increased core body temperature CARDIOVASCULAR RESPONSES TO changes in body temperature include marked changes in sympathetic nerve activity and blood flow. In response to hyperthermia, for example, there are increases in splanchnic, renal, splenic, and lumbar sympathetic nerve activity (25,28), resulting in vasoconstriction of the respective vascular beds. In contrast, hyperthermia elicits vasodilation in the skin vasculature, and in the rat tail vasodilation also occurs (21, 24); the tail is a major thermoregulatory organ in the rat. These changes contribute to the redistribution of the blood flow during hyperthermia such that blood is redirected from the warm internal environment in visceral organs to the peripheral vasculature where heat can be dissipated.The alterations in blood flow, mediated by changes in sympathetic nerve activity, involve the central nervous system. The sites in the brain that are likely to be involved in mediating the responses include the sympathetic premotor nuclei located in the hypothalamus and brain stem. These regions contain neurons that directly project to the sympathetic preganglionic motor neurons located in the intermediolateral cell column of the thoracolumbar spinal cord.Within the forebrain, the hypothalamic paraventricular nucleus (PVN) is a key integrative site involved in hormonal, endocrine, and neural control. The PVN is composed of different neuronal subgroups subserving different functions, including cardiovascular regulation. The PVN is one of the small number of premotor nuclei present in the brain (4, 47). There are neurons in the PVN that project to regions of the spinal cord where sympathetic preganglionic neurons are located and thereby can directly influence sympathetic activity (8,40,48). In addition to the spinal projecting neurons present in the PVN, there are neuronal sub...

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

“…Neurons in the PVN are activated by increases in ambient temperature, including those that influence sympathetic nerve activity (3,7,9,27), suggesting a role for the PVN in temperature regulation. The present study, together with our more recent work showing that inhibition of neuronal function within the PVN prevented the hyperthermia-induced reduction in renal and mesenteric blood flows, provides direct evidence that the PVN plays a key role in the cardiovascular thermoregulatory responses (8,10). This does not exclude other brain regions contributing to the reflex renal vasoconstriction elicited by hyperthermia.…”

“…Our hypothesis is that the PVN is the key site, since it has a dense concentration of ANG II type 1 receptors and that inhibition of the PVN prevents the reflex vasoconstriction in renal and mesenteric vasculature (1,8,10). In the present study, therefore, we investigated the effect of microinjection of the ANG II type 1 receptor antagonist, losartan, directly into the PVN on the reflex reduction in renal blood flow induced by elevating body core temperature in rats.…”

“…More recently, we have found that the PVN is essential for the normal reflex reduction in renal and mesenteric blood flows induced by hyperthermia (6,8,10). The PVN is one of the few sympathetic premotor nuclei present in the brain; that is, it contains neurons that project directly to sympathetic preganglionic motor neurons in the intermediolateral cell column of the thoracolumbar spinal cord (9, 32, 36).…”

Central blockade of nitric oxide transmission impairs exercise-induced neuronal activation in the PVN and reduces physical performance

“…Rats that were directly injected in the PVN with muscimol, which is a GABA-ergic agonist employed to inhibit neuronal function, did not show the classical response of blood flow redirection in response to hyperthermia Chen et al, 2008). Following the same protocol, intra-PVN administration of L-NAME also prevented the redirection of blood flow (Chen et al, 2010).…”

Role of the hypothalamic PVN in the regulation of renal sympathetic nerve activity and blood flow during hyperthermia and in heart failure

“…Recent studies have highlighted the essential role of the PVN in the reduction in mesenteric and renal blood flows induced by hyperthermia (9,11). Inhibition of neuronal function within the PVN using the GABA A agonist muscimol prevented the normal reduction in mesenteric blood flow, and the effect was specific to the PVN (11).…”