title: Effects of hypercapnia on prostanoid and cAMP production by cerebral microvascular cell cultures.
abstract: In the newborn pig cerebral circulation, arteriolar dilation in response to hypercapnia requires the presence of intact endothelium and is accompanied by an indomethacin-sensitive increase in cortical adenosine 3',5'-cyclic monophosphate (cAMP). The effects of short-term hypercapnia on production of dilator prostanoids and cAMP were investigated using newborn pig cerebral microvascular smooth muscle cells and endothelial cells cultured both separately and in noncontact coculture. Microvascular smooth muscle cells respond to hypercapnia (pH 7.00 +/- 0.05 PCO2 75 +/- 3 mmHg) by a 1.3- to 1.7-fold increase in basal cAMP production that is not affected by indomethacin, whereas hypercapnia and 80 mM sodium propionate do not affect iloprost-stimulated cAMP production. Microvascular endothelial cells cultured on Millicel inserts respond to hypercapnia by a two- to fourfold increase in prostacyclin (as 6-keto-prostaglandin F1 alpha) and prostaglandin E2 production in both luminal and abluminal compartments. For noncontact coculture, Millicel inserts with endothelial cells (as hypercapnia-sensitive producers of prostanoids) were installed into cell culture dishes with aspirin-pretreated smooth muscle cells (as targets for endothelium-derived dilator prostanoids). Exposure of noncontact microvascular cell cocultures to hypercapnia results in a three- to fourfold stimulation of prostanoid and cAMP production. Therefore, short-term hypercapnia increases cAMP production by microvascular smooth muscle cells via 1) a direct (prostanoid independent) mechanism and 2) an endothelial-dependent pathway that involves prostanoids. Endothelium-produced prostanoid signals are necessary for a full increase in cAMP production by cerebral microvascular smooth muscle cells in response to hypercapnia.
authors.affiliation: Department of Physiology and Biophysics, University of Tennessee, Memphis 38163, USA.
authors.forename: H
authors.initials: H
authors.lastname: Parfenova
authors.forename: C W
authors.initials: CW
authors.lastname: Leffler
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation; D018920:Coculture Techniques; D003470:Culture Media / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006935:Hypercapnia / Q000378:metabolism*; D008833:Microcirculation; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D003470:Culture Media; D011422:Propionates; D011453:Prostaglandins; D014665:Vasodilator Agents; C514135:sodium propionate; D000242:Cyclic AMP; C029658:propionic acid