Vasoconstrictive peptides induce endothelin-1 and prostanoids in human cerebromicrovascular endothelium.
Vasoconstrictive peptides and prostanoids have been implicated in the pathogenesis of hypertension and vasospasm. Recently, we have shown that human cerebromicrovascular endothelium [human brain endothelial cells (HBEC)] constitutively produces both endothelin-1 (ET-1) and prostanoids. The vasoactive peptides, arginine vasopressin (AVP) or angiotensin II (ANG II), stimulated secretion of both immunoreactive ET-1 and prostanoids from HBEC by a receptor-mediated induction of phospholipase C (PLC) and PLA2. The release of constitutive or AVP- or ANG II-induced ET-1 occurred at different rates during the 24-h incubation of HBEC in serum-free medium. The temporal profile of AVP-stimulated production of prostanoids differed from that of ANG II. AVP-induced release of prostaglandin D2 (PGD2) persisted for 24 h, whereas ANG II-stimulated PGD2 was only seen during the first 4 h of incubation. ANG II maximally stimulated PGI2 secretion during the 4- to 8-h interval, whereas AVP did not stimulate PGI2 secretion. Dexamethasone (Dxm), indomethacin (Indo), and nordihydroguaiaretic acid, the respective inhibitors of PLA2-cyclooxygenase II, cyclooxygenase, and lipoxygenase, increased both constitutive and AVP- or ANG II-stimulated secretion of ET-1. Dxm also decreased AVP- or ANG II-stimulated production of PGD2 and PGF2 alpha. These results indicate an interrelationship between HBEC production of ET-1 and prostanoids, which may play a role in regulating cerebral microcirculation.
Spatz
M
M
Stroke Branch, National Institute of Neurological Disorders and Stroke, Bethesda 20892.
Stanimirovic
D
D
Bacic
F
F
Uematsu
S
S
McCarron
R M
RM
D000804:Angiotensin II / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D001127:Arginine Vasopressin / Q000494:pharmacology; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology; D016232:Endothelins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D016232:Endothelins; D010455:Peptides; D011453:Prostaglandins; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D001127:Arginine Vasopressin; D016718:Arachidonic Acid; D003907:Dexamethasone; D015544:Inositol 1,4,5-Trisphosphate