ROLE OF CEREBRAL ATP‐SENSITIVE K⁺ CHANNELS IN ARTERIAL PRESSURE REGULATION DURING ACUTE CEREBRAL ISCHAEMIA IN SHR AND WKY RATS

Abstract

1. ATP-sensitive K+ channels ( K m ) are activated either by decreased intracellular ATP content or ATP/ ADP ratio during ischaemia. We examined the role of a cerebral KATP in arterial pressure regulation during acute cerebral ischaemia using SHR and WKY rats. Thirteen week old male SHR or WKY rats were anaesthetized with urethane, and arterial pressure and heart rate were recorded under an artificial ventilation.2. Intracerebroventricular (i.c.v.) injections of glibenclamide, a specific inhibitor of K m , elicited dose-dependent vasopressor responses in WKY with bilateral ligation of carotid arteries, whereas it caused smaller vasopressor responses in SHR than WKY.3. Systemic administration of AVP VI receptor antagonist, OPC-21268, abolished the vasopressor responses of i.c.v. injections of glibenclamide in WKY but not in SHR.4. Intracerebroventricular injections of glibenclamide caused both the increase in plasma concentration of AVP and the decrease in pituitary AVP content in WKY with bilateral ligation of carotid arteries, whereas it elicited no significant change in plasma and pituitary concentration of AVP in SHR with bilateral ligation of carotid arteries. 5. Cerebral Kmp may play a role in the protection of excess hypertension by inhibiting AVP release from the pituitary glands during acute ischaemia in WKY, but this mechanism might not work in SHR during acute cerebral ischaemia.

KATP channels are regulators of programmed cell death and targets for the creation of novel drugs against ischemia/reperfusion cardiac injury

“…Neurons in the posterior hypothalamus and their KATP channels are involved in the cardiovascular regulation [40]. Intracerebroventricular administration of glibenclamide resulted in dose‐dependent vasopressor responses in rats [41]. Consequently, it could be proposed that some cardiovascular effects of KCOs could be mediated via the opening of neuronal KATP channels.…”

Patents related to therapeutic activation of KATPand K2Ppotassium channels for neuroprotection: ischemic/hypoxic/anoxic injury and general anesthetics

“…However, by means of K ATP openers like diazoxide (known to stimulate insulin secretion) it is channel activation that is thought to confer cardio-and neuroprotection [18,20]. The neuroprotective effects of K ATP openers in conditions of cellular insults and injury such as ischemic/hypoxic/anoxic conditions, like iptakalim [21], arise from suppression of seizure propagation, suggesting a role for K ATP channels in acquired brain tolerance or 'preconditioning' as a neuroprotection mechanism [22][23][24][25][26][27][28][29][30], including inhalation anesthetic (i.e., sevoflurane, halothane and xenon preconditioning) [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49], and as brain glucose metabolic sensors in hyperglycemia and hypoglycemia (i.e., brain regions of important K ATP expression include neurons in the hippocampus, hypothalamus, dorsal vagal nerve, substantia nigra, neocortex, and in glial cells). As K ATP channels contribute to regulation of food intake and body weight [50][51][52][53], they are also implicated in the development of obesity and diabetes.…”