The role of prostanoids in the mediation of responses to KC-404, a novel cerebrovasodilator

W. M. Armstead, R. Mirro, Charles Leffler, D. W. Busija

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Abstract

The purpose of this study was to characterize the nature of the response to KC-404 in the cerebral microcirculation of the newborn pig. Pial arterioles were observed directly using a closed cranial window in choralose-anesthetized piglets. Topical application of 100, 300, 1000, 3000 and 10,000 ng/ml of KC-404 produced concentration-dependent increases in pial arteriolar diameter. Diameters were 168 ± 18, 190 ± 19 and 238 ± 21 μ for control, 100 ng/ml and 10,000 ng/ml of KC-404, respectively. Responses to KC-404 (3-isobutyryl-2-isopropylpyrazolo-[1,5a]-pyridine) were blocked by indomethacin (5 mg/kg i.v.). Moreover, KC-404, topically applied to the cerebral cortex, produced small but significant increases in cortical subarachnoid cerebrospinal fluid levels of 6-keto-prostaglandin (PG) F(1α) and PGE2, whereas thromboxane B2 levels were unchanged. Similar to topical application, i.v. KC-404 (0.5 mg/kg) produced pial arteriolar dilation without significantly altering arterial blood pressure. Intravenous KC-404 also increased cerebrospinal fluid levels of 6-keto-PGF(1α) and PGE2, whereas thromboxane levels were unchanged. Further, topically applied KC-404 (1 μg/ml) potentiated dilator responses to PGE2 and PGI2, whereas responses to isoproterenol were unchanged. These data indicate that KC-404 is a potent dilator of cerebral arterioles in newborn pigs. These data also suggest that KC-404 produces cerebral vasodilation predominantly by potentiating prostanoid-mediated dilation.

Original languageEnglish (US)
Pages (from-to)138-143
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume244
Issue number1
StatePublished - 1988

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Prostaglandins
Dinoprostone
Arterioles
Prostaglandins F
Cerebrospinal Fluid
Dilatation
Swine
ibudilast
Thromboxane B2
Thromboxanes
Epoprostenol
Microcirculation
Isoproterenol
Vasodilation
Indomethacin
Cerebral Cortex
Arterial Pressure

All Science Journal Classification (ASJC) codes

  • Pharmacology

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The role of prostanoids in the mediation of responses to KC-404, a novel cerebrovasodilator. / Armstead, W. M.; Mirro, R.; Leffler, Charles; Busija, D. W.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 244, No. 1, 1988, p. 138-143.

Research output: Contribution to journalArticle

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