Vasodilation induced by oxygen/glucose deprivation is attenuated in cerebral arteries of SUR2 null mice.

Abstract

Physiological functions of arterial smooth muscle cell ATP-sensitive K(+) (K(ATP)) channels, which are composed of inwardly rectifying K(+) channel 6.1 and sulfonylurea receptor (SUR)-2 subunits, during metabolic inhibition are unresolved. In the present study, we used a genetic model to investigate the physiological functions of SUR2-containing K(ATP) channels in mediating vasodilation to hypoxia, oxygen and glucose deprivation (OGD) or metabolic inhibition, and functional recovery following these insults. Data indicate that SUR2B is the only SUR isoform expressed in murine cerebral artery smooth muscle cells. Pressurized SUR2 wild-type (SUR2(wt)) and SUR2 null (SUR2(nl)) mouse cerebral arteries developed similar levels of myogenic tone and dilated similarly to hypoxia (<10 mmHg Po(2)). In contrast, vasodilation induced by pinacidil, a K(ATP) channel opener, was ∼71% smaller in SUR2(nl) arteries. Human cerebral arteries also expressed SUR2B, developed myogenic tone, and dilated in response to hypoxia and pinacidil. OGD, oligomycin B (a mitochondrial ATP synthase blocker), and CCCP (a mitochondrial uncoupler) all induced vasodilations that were ∼39-61% smaller in SUR2(nl) than in SUR2(wt) arteries. The restoration of oxygen and glucose following OGD or removal of oligomycin B and CCCP resulted in partial recovery of tone in both SUR2(wt) and SUR2(nl) cerebral arteries. However, SUR(nl) arteries regained ∼60-82% more tone than did SUR2(wt) arteries. These data indicate that SUR2-containing K(ATP) channels are functional molecular targets for OGD, but not hypoxic, vasodilation in cerebral arteries. In addition, OGD activation of SUR2-containing K(ATP) channels may contribute to postischemic loss of myogenic tone.

• Authors: Adebowale Adebiyi, Elizabeth M McNally, Jonathan H Jaggar
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 301 Issue 4 Pg. H1360-8 (Oct 2011) ISSN: 1522-1539 [Electronic] United States
• PMID: 21784985 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• ABCC9 protein, human
• ATP-Binding Cassette Transporters
• Abcc9 protein, mouse
• KATP Channels
• Potassium Channels, Inwardly Rectifying
• Receptors, Drug
• Sulfonylurea Receptors
• Vasodilator Agents
• Pinacidil
• Adenosine Triphosphate
• Glucose

Topics

• ATP-Binding Cassette Transporters (genetics, physiology)
• Adenosine Triphosphate (biosynthesis)
• Animals
• Blotting, Western
• Cerebral Arteries (anatomy & histology, physiology)
• Female
• Glucose (deficiency)
• Homeostasis
• Hypoxia (genetics, physiopathology)
• KATP Channels (physiology)
• Male
• Mice
• Mice, Knockout
• Mitochondria (metabolism)
• Myocytes, Smooth Muscle (metabolism)
• Pinacidil (pharmacology)
• Potassium Channels, Inwardly Rectifying (genetics, physiology)
• Receptors, Drug (genetics, physiology)
• Reverse Transcriptase Polymerase Chain Reaction
• Sulfonylurea Receptors
• Vasodilation (genetics, physiology)
• Vasodilator Agents (pharmacology)