Initiation of remote microvascular preconditioning requires K_ATP channel activity

Abstract

The purpose of this study was to investigate vascular preconditioning of individual microvascular networks. Prior work shows that exposure of downstream arterioles to specific agonists preconditions upstream arterioles so that they exhibit an altered local vasoactive response [remote microvascular preconditioning (RMP)]. We hypothesized that mitochondrial ATP-sensitive K+ (K(ATP)) channels were involved in stimulation of RMP. Arteriolar diameter (approximately 15 microm) was observed approximately 1,000 microm upstream of the remote exposure site in the cheek pouch of pentobarbital sodium-anesthetized (70 mg/kg) male hamsters (n = 104); all agonists were applied via micropipette. RMP was initiated by application of pinacidil (Pin), diazoxide (DZ), sodium nitroprusside (SNP), or bradykinin (BK) to the downstream vessel. After 15 min, RMP was apparent at the upstream observation site from testing of local vasoactive responses to L-arginine. Pin, DZ, SNP, and BK each stimulated RMP. To evaluate a specific role for mitochondrial K(ATP) channels in this response, 5-hydroxydecanoate was applied (via a 2nd pipette) during downstream stimulation with agonist. 5-Hydroxydecanoate blocked RMP initiated by Pin, DZ, or SNP, suggesting that mitochondrial K(ATP) channels are involved before SNP signal transduction. To verify this, we applied N(omega)-nitro-L-arginine during DZ or SNP stimulation. RMP was blocked during SNP, but not during DZ, stimulation. Thus stimulation of the RMP response requires mitochondrial K(ATP) channel activity after stimulation by nitric oxide donors.

In Vitro Hematological and In Vivo Vasoactivity Assessment of Dextran Functionalized Graphene

“…Thus, the exposure time of the GNP-Dex was extended to 30 seconds. Finally, testing the range of concentrations is critical since it is well known that long-lasting pro-inflammatory responses can be induced if inflammatory agents are exposed to the vasculature even briefly (seconds)474849505152. The exposure to GNP-Dex to the terminal or arcade arterioles caused a dose dependent dilation and yielded statistically similar EC 50 (half of maximal dilation observed, noted on Figure 7B) and maximal dilation values in both.…”

“…Male hamsters (100 ± 4 days, mean ± SD, 112.5 ± 10 grams, n = 8) were anesthetized with isoflurane (4% induction, 1% thereafter). The left cheek pouch tissue was exteriorized, pinned across a Lucite pedestal and cleared of connective tissue48515255. Physiological saline flowed over the exteriorized tissue (5 ml/min).…”

Vasoactive effects of stable aqueous suspensions of single walled carbon nanotubes in hamsters and mice

“…In the hamster, the left cheek pouch tissue was prepared, as previously. (Frame and Mabanta, 2007, Frame et al, 2007, Mabanta et al, 2006, Mustafa et al, 1999) In the mouse, the right cremaster muscle was prepared, as previously. (Georgi et al, 2011b) For each, the tissue was pinned across a quartz pedestal with warmed superfusate (physiological saline) flowing over the flat tissue at a rate of 5 ml/min.…”

Remote Ischemic Preconditioning: A Novel Protective Method From Ischemia Reperfusion Injury—A Review

“…Dickson et al showed blockade of K ATP channels abolished transferred preconditioning in virgin hearts conferred by coronary effluent from preconditioned hearts [66]. Mabanta et al showed that remote microvascular preconditioning is mediated by K ATP channels and blockade of K ATP channels abolished preconditioning [129]. Pell et al showed renal IR (10 min cycles) reduced myocardial infarct size and cardioprotection was abolished by K ATP blockers (5-HD) [27].…”