Subarachnoid hematoma attenuates vasodilation and potentiates vasoconstriction induced by vasoactive agents in newborn pigs.
The effects of perivascular blood on pial arteriolar vasoreactivity to selected vasodilators and vasoconstrictors were examined in vivo in a newborn pig model. alpha-Chloralose-anesthetized newborn pigs were fitted with closed cranial windows 4 d after cortical subarachnoid injections of autologous blood. The responsiveness of pial arterioles to topical application of dilator agents [iloprost, prostaglandin E2 (PGE2), histamine, and sodium nitroprusside (SNP)] and vasoconstrictor agents [leukotriene C4 and endothelin-1 (ET-1) in artificial cerebrospinal fluid was studied in control and blood-injected piglets. Pial arterioles dilated dose dependently in response to topical application of iloprost, PGE2, histamine, and SNP in the control group, with increases in diameter of 54, 44, 67, and 50% at 10(-8) M, 10(-5) M, 10(-5) M, and 10(-5) M, respectively. These dilations in response to iloprost, PGE2, and histamine in the blood-injected piglets were significantly attenuated to 23, 18, and 34%, respectively, whereas the dilation in response to SNP was not changed (64%). Constrictions in response to 10(-8) M leukotriene C4 and ET-1 were 16 and 26% and were potentiated by hematoma to 36 and 43%, respectively. The lowest dose of ET-1 (10(-12) M) significantly dilated pial arterioles in the control but not in the blood-treated group. We conclude that prolonged exposure of pial arterioles to perivascular blood attenuates cerebrovascular dilation in response to selected vasoactive agents (iloprost, PGE2, and histamine) but not to SNP, suggesting that blood-induced attenuation of vasodilation and the generalized vasoconstriction may involve inhibiting the prostanoid/cAMP signaling pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
Yakubu
M A
MA
Department of Physiology and Biophysics, University of Tennessee, Memphis 38163.
Shibata
M
M
Leffler
C W
CW
D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000187:drug effects; D016232:Endothelins / Q000494:pharmacology; D006406:Hematoma / Q000097:blood / Q000503:physiopathology*; D015289:Leukotrienes / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology; D013345:Subarachnoid Hemorrhage / Q000097:blood / Q000503:physiopathology*; D013552:Swine; D014661:Vasoconstriction / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
D016232:Endothelins; D015289:Leukotrienes; D011453:Prostaglandins