Reversal by increased CSF [H+] and [K+] of phorbol ester-induced arteriolar constriction in piglets.
We determined whether several dilator stimuli could counteract phorbol ester-induced constriction of pial arterioles. A closed cranial window was implanted, and the diameter of one pial arteriole was determined by intravital microscopy in newborn pigs. Diameter of one pial arteriole was determined during baseline conditions and topical application of 10(-5) M phorbol 12, 13-dibutyrate (PDB) and during subsequent application of one of the following: arterial hypercapnia (inhalation of 10% CO2), topical application of cerebrospinal fluid with 12 mM K+, or topical application of 10(-5) M isoproterenol in cerebrospinal fluid. PDB constricted the arterioles from 101 +/- 5 to 70 +/- 5 microns (27 +/- 4%; n = 28). During this period of constriction which lasted longer than subsequent interventions (> 90 min), arterial hypercapnia dilated the arterioles by 85 +/- 19% (n = 12), and topical 12 mM K+ dilated the arterioles by 59 +/- 12% and caused vasomotion (n = 7). Despite blockade of direct dilator effects of arterial hypercapnia by indomethacin, arterial hypercapnia still reversed phorbol ester-induced constriction, suggesting that acidosis by itself is sufficient to cause this effect. In contrast, topical isoproterenol did not dilate PDB-constricted arterioles (n = 9); however, topical forskolin (2.4 x 10(-7) M) did reverse constriction, implying that protein kinase C activation may interfere with proper functioning of the beta-adrenoceptor. Therefore, increased extracellular fluid levels of K+ and H+, but not isoproterenol, are able to interfere with cerebrovascular consequences of protein kinase C activation.
Busija
D W
DW
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157.
Chen
J
J
D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D005576:Colforsin / Q000494:pharmacology; D006859:Hydrogen / Q000134:cerebrospinal fluid*; D006935:Hypercapnia / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D009994:Osmolar Concentration; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D010841:Pia Mater / Q000098:blood supply*; D011188:Potassium / Q000134:cerebrospinal fluid*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation
D005576:Colforsin; D015240:Phorbol 12,13-Dibutyrate; D006859:Hydrogen; D007545:Isoproterenol; D011188:Potassium; D007213:Indomethacin