Effects of hypercapnia on dilator prostanoid and cyclic amp production by cerebral microvascular endothelial and smooth muscle cell cultures. Parfenova, Helena, and Charles W. Leffler. Laboratory for Research in Neonatal Physiology, Departments of Physiology and Biophysics and Pediatrics, University of Tennessee, Memphis, TN 38163
APStracts 2:0455C, 1995.
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 cyclic AMP. The effects of short-term hypercapnia on production of dilator prostanoids and cyclic AMP 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 mm Hg) by a 1.3-1.7 fold increase in basal cyclic AMP production that is not affected by indomethacin, while hypercapnia and 80 mM sodium propionate do not affect iloprost-stimulated cyclic AMP production. Microvascular endothelial cells cultured on Millicel -CM inserts respond to hypercapnia by a 2-4 fold increase in prostacyclin (as 6-keto-PGF1[alpha]) and PGE2 production in both luminal and abluminal compartments. For noncontact coculture, Millicel-CM 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 3-4 fold stimulation of prostanoid and cyclic AMP production. Therefore, short-term hypercapnia increases cyclic AMP 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 cyclic AMP production by cerebral microvascular smooth muscle cells in response to hypercapnia. 

Received 17 July 1995; accepted in final form 1 December 1995.
APS Manuscript Number C432-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 December 95