title: Hypotension dilates pial arteries by KATP and kca channel activation.
abstract: Hypotension induced pial artery dilation is prostaglandin-dependent in the newborn pig. Prostaglandins, in turn, elicit vasodilation through cGMP and cAMP dependent mechanisms and K+ channel activation contributes to cyclic nucleotide induced vasodilation. The present study was designed to characterize the role of ATP sensitive (KATP) and calcium sensitive (Kca) channel activation in hypotension induced pial artery dilation in newborn pigs equipped with a closed cranial window. Glibenclamide and iberiotoxin, KATP and Kca channel antagonists, attenuated hypotension induced dilation (36+/-1 vs. 14+/-2% before and after iberiotoxin). Combined administration of these K+ channel antagonists eliminated the vascular response. Hypotension induced dilation was associated with elevated cerebrospinal fluid (CSF) cAMP but not cGMP concentration (1023+/-29 vs. 1566+/-39 fmol/ml for cAMP). L-NNA, a nitric oxide (NO) synthase inhibitor, and Rp 8-Br cGMPs, a protein kinase G inhibitor, had no effect but Rp 8-Br cAMPs, a protein kinase A inhibitor, attenuated hypotensive dilation (35+/-1 vs. 16+/-2% before and after Rp 8-Br cAMPs). Dilation by the cAMP analogue 8-Bromo cAMP (10(-8), 10(-6) M) was attenuated by glibenclamide and iberiotoxin (8+/-1 and 17+/-1 vs. 4+/-1 and 9+/-1% before and after glibenclamide). These data show that both KATP and Kca channel activation contribute to hypotension induced dilation. These data suggest that dilation during hypotension results from the sequential release of prostaglandins and cAMP, which, in turn, activates both the KATP and Kca channel.
authors.affiliation: Department of Anesthesia, 34th and Civic Center Blvd., The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: Armstead
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001158:Arteries; D002118:Calcium / Q000502:physiology*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D007022:Hypotension / Q000503:physiopathology*; D015640:Ion Channel Gating / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply*; D015221:Potassium Channels / Q000378:metabolism* / Q000502:physiology; D013552:Swine; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D010455:Peptides; D015221:Potassium Channels; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009569:Nitric Oxide; C064719:iberiotoxin; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D006152:Cyclic GMP; D005905:Glyburide; D002118:Calcium