title: Stimulus duration-dependent contribution of k(ca) channel activation and cAMP to hypoxic cerebrovasodilation.
abstract: Activation of calcium sensitive (K(ca)) K channels and cAMP contribute to pial artery dilation observed during a 10-min exposure to hypoxia. Recent studies show that pial dilation during a 20- or 40-min hypoxic exposure was less than that observed during a 5- or 10-min exposure indicating that stimulus duration determines the nature of the vascular response to hypoxia. The present study was designed to determine if the stimulus duration modulates the contribution of K(ca) channel activation and cAMP-dependent mechanisms to hypoxic pial artery dilation in piglets equipped with a closed cranial window. The K(ca) channel antagonist iberiotoxin had no influence on pial dilation during 5 min of hypoxia (pO(2) approximately 25 mmHg), decremented the dilation during 10- and 20-min exposure, but had no effect on the dilation during a 40-min exposure (33+/-1% vs. 32+/-3%, 33+/-1% vs. 25+/-1%, 23+/-1% vs. 19+/-1%, and 21+/-2% vs. 17+/-2% for 5-, 10-, 20-, and 40-min hypoxic dilations before and after iberiotoxin). NS1619, a K(ca) channel agonist, induced pial dilation during hypoxia that was attenuated by 20- and 40-min but not by 5- and 10-min exposure durations. Similarly, the cAMP antagonist Rp 8-Bromo cAMPs had no influence on pial dilation during 5 min of hypoxia, decremented the dilation during a 10-min exposure, but had no effect on the dilation during a 20- or 40-min exposure (36+/-1% vs. 34+/-2%, 34+/-1% vs. 22+/-1%, 24+/-2% vs. 21+/-2%, and 21+/-2% vs. 19+/-2% for 5-, 10-, 20-, and 40-min hypoxic dilations before and after Rp 8-Bromo cAMPs). Additionally, CSF cAMP was unchanged during 5 min, elevated during 10 min, but such elevations were attenuated during 20- and 40-min hypoxic exposure. Pial vasodilation to a cAMP analogue during hypoxia was attenuated by 20- and 40-min but not by 5- and 10-min hypoxic exposure durations. These data show that K(ca) channel activation and cAMP contribute to hypoxic pial artery dilation in a stimulus duration-dependent manner. These data suggest that diminished pial artery dilation during longer hypoxic exposure results from attenuated K(ca) channel and cAMP-dependent mechanisms.
authors.affiliation: Department of Anesthesia, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Ben-Haim
authors.forename: W M
authors.initials: WM
authors.lastname: Armstead
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000134:cerebrospinal fluid / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D002534:Hypoxia, Brain / Q000378:metabolism*; D008297:Male; D009479:Neuropeptides / Q000134:cerebrospinal fluid; D010208:Papaverine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010812:Physical Stimulation; D010841:Pia Mater / Q000098:blood supply; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000819:agonists / Q000378:metabolism*; D013552:Swine; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: C105593:8-bromoadenosine-3',5'-cyclic monophosphorothioate; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D009479:Neuropeptides; D010455:Peptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013873:Thionucleotides; D014665:Vasodilator Agents; C086491:NS 1619; D015124:8-Bromo Cyclic Adenosine Monophosphate; C064719:iberiotoxin; D010208:Papaverine; D000242:Cyclic AMP