Vasopressin Inhibits Sarcolemmal ATP-Sensitive K+ Channels via V1 Receptors Activation in the Guinea Pig Heart.

Abstract

asopressin is one of the physiologically active peptides that regulate humoral immunity by promoting reabsorption of water in the kidney and simultaneously having a potent vasoconstrictive action on vascular smooth muscle by increasing the production of inositol 1,4,5-triphosphate (IP3) and 1,2-diacylglycerol (DG) and activating the voltage-dependent Ca channel, which results in elevation of the intracellular Ca concentration. 1,2 Recently, it has been reported that secretion of vasopressin increases in pathophysiological conditions such as angina pectoris, acute myocardial infarction and chronic heart failure. 3 During such conditions of metabolic inhibition, activation of the sarcolemmal KATP channel 4 is known to regulate Ca 2+ entry and myocardial contractility in order to lessen the myocardial damage. 5,6 Moreover, activation of this channel minimizes the infarct area in animal models 7 and elicits a cardioprotective action in dogs with pacinginduced heart failure. 8 On the other hand, its activation has been reported to shorten the action potential duration, thereby in part acting arrhythmogenically in acute ischemia. 9,10 Moreover, Martin et al 2 reported that vasopressin inhibited the sarcolemmal KATP channels and activated the voltage-dependent Ca channel, thereby regulating insulin secretion in rat pancreatic -cells. Wakatsuki et al 11 reported that vasopressin activated Ca-activated K channels and simultaneously controlled vascular tone by suppressing sarcolemmal KATP channels in porcine coronary vascular smooth muscle cells in the cell-attached configuration. More recently, it has been reported that the vasopressin V1 Circulation Journal Vol.66, March 2002receptor couples to protein kinase C via activation of phospholipase C and that vasopressin V2 receptor links to G protein coupled protein kinase including adenylate cyclase. [12][13][14][15] In the central nervous system, Easaw 16 showed that vasopressin-inhibited the voltage-dependent outward current via the V1 receptor, and it activated the same current via the V2 receptor.Therefore vasopressin regulates excitation of neurons in a diagonal band of the rat. However, the action of vasopressin in the heart still remains controversial. The present study aimed to examine the physiological implication of vasopressin's effects on sarcolemmal KATP channel in enzymatically isolated guinea pig ventricular myocytes using both cell-attached and inside-out configurations. Methods Preparation of Single Ventricular CardiomyocytesAdult male guinea pigs of 250-300 g were anesthetized with pentobarbital sodium (40-50 mg/kg ip) and isolated ventricular cells were obtained using the collagenase perfusion method. 17 In brief, the chest was briefly opened under artificial ventilation, the aorta cannulated and the heart quickly dissected. Using a Langendorff apparatus, the heart was retrogradedly perfused with normal Tyrode's solution for about 5 min to wash out the blood in the vessels, followed by nominally Ca 2+ -free Tyrode's solution for about 3 min at 36°C. The h...

Arginine vasopressin inhibits Kir6.1/SUR2B channel and constricts the mesenteric artery via V1a receptor and protein kinase C

“…Accumulating experimental evidence indicates that K ATP channels are inhibited by AVP leading to depolarization. In guinea pig ventricular myocytes, AVP inhibits K ATP channels through V1a receptors with an IC 50 of 15 nM (36). In the RINm5F insulin-secreting cell line, AVP inhibits K ϩ channels that are closed by tolbutamide and opened by diazoxide (21), suggesting that the Kir6.2/SUR1 channel is involved.…”

“…However, the modulation of the vascular K ATP channels by AVP is still controversial (6,38). There is evidence that K ATP channels in cardiac myocytes and the insulinoma cell line are also inhibited by AVP, suggesting that Kir6.2/SUR1 and Kir6.2/SUR2A channels are targeted (21,36). Since functional vascular K ATP channels are mainly made of Kir6.1 with SUR2B subunits, the understanding of K ATP channel contribution to vascular tones relies on the demonstration of the precise signal network between neurotransmitters/hormones and K ATP channels.…”

Vasopressin: Mechanisms of action on the vasculature in health and in septic shock

“…Inhibition of these channels could therefore help to restore normal vascular reactivity (37, 79). In vitro work in cultured porcine vascular smooth muscle cells and isolated cardiac myocytes has demonstrated the ability of vasopressin to close K ATP channels (80,81). This effect was blocked by selective inhibition of PKC (81), which may act by direct phosphorylation of the channel (82) or by increasing sarcolemmal ATP (81).…”

Resuscitation after cardiac arrest in a septic porcine model: adding vasopressin vs epinephrine alone administration

“…Also, AVP administration inhibited NO production induced by LPS infusion [30] and restored LPS-induced vascular hyporeactivity [31-33]. …”