Prostanoids promote pial arteriolar dilation and mask constriction to oxytocin in piglets.
We determined effects of oxytocin on piglet pial arterioles and the role of prostanoids in mediating arteriolar responses. Anesthetized piglets were equipped with closed cranial windows, and arteriolar diameter was measured using intravital microscopy. Pial arterioles were exposed to 10(-10) to 10(-4) M oxytocin. Cerebrospinal fluid (CSF) levels of prostaglandin E2 (PGE2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) were determined using radioimmunoassay. Baseline diameter was 110 +/- 4 microns and increased to 120 +/- 6 microns at 10(-8) M (9 +/- 3%, n = 20). CSF levels of PGE2 were 697 pg/ml during baseline and increased to 1,685 +/- 316 pg/ml during 10(-6) M, 2,243 +/- 327 pg/ml during 10(-5) M, and 2,941 +/- 500 pg/ml during 10(-4) (n = 6). CSF levels of 6-keto-PGF1 alpha were 354 +/- 73 pg/ml during baseline and increased to 734 +/- 168 pg/ml at 10(-5) M and to 836 +/- 167 pg/ml at 10(-4) M (n = 5). After inhibition of prostaglandin synthesis by indomethacin (5 mg/kg i.v.), oxytocin constricted at all doses, starting at 10(-10) M (5 +/- 2%) and continuing to constrict at 10(-4) M (24 +/- 2%, n = 14). We conclude that: 1) piglet pial arterioles respond to relatively low levels of oxytocin, 2) local presence and/or production of prostanoids promotes dilation, and 3) endogenous prostanoids prevent constriction of pial arterioles to oxytocin. Our results suggest that oxytocin could play a role in the regulation of cerebral hemodynamics.
Busija
D W
DW
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157-1083.
Khreis
I
I
Chen
J
J
D015121:6-Ketoprostaglandin F1 alpha / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015232:Dinoprostone / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007213:Indomethacin / Q000494:pharmacology; D008853:Microscopy / Q000379:methods; D010121:Oxytocin / Q000494:pharmacology*; D010841:Pia Mater / Q000098:blood supply*; D011863:Radioimmunoassay; D013552:Swine / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D010121:Oxytocin; D015121:6-Ketoprostaglandin F1 alpha; D001120:Arginine; D015232:Dinoprostone; D007213:Indomethacin