nitroarginine and carboprostacyclin

Nitric oxide and prostaglandins were shown to contribute to the endothelial mediation of flow-induced dilation of skeletal muscle arterioles of rats. Thus, we hypothesized that flow-induced dilation and its mediation are altered in gracilis muscle arterioles of mice deficient in the gene for endothelial nitric oxide synthase (eNOS-KO) compared with control wild-type (WT) mice. Gracilis muscle arterioles ( approximately 80 micrometer) of male mice were isolated, then cannulated and pressurized in a vessel chamber. The increases in diameter elicited by increases in perfusate flow from 0 to 10 microq/min were similar in arterioles from eNOS-KO (n=28) and WT (n=22) mice ( approximately 20 micrometer at 10 microL/min flow). Removal of the endothelium eliminated flow-induced dilations in vessels of both strains of mice. N(omega)-nitro-L-arginine (L-NNA, 10(-4) mol/L) significantly inhibited flow-induced dilation in arterioles of WT mice by approximately 51% but had no effect on responses of arterioles from eNOS-KO mice. Indomethacin (INDO, 10(-5) mol/L) inhibited flow-induced dilation of WT mice by approximately 49%, whereas it completely abolished this response in arterioles of eNOS-KO mice. Simultaneous administration of INDO and L-NNA eliminated flow-induced responses in arterioles of WT mice. Dilations to carbaprostacyclin were similar at concentrations of 10(-8) and 3x10(-8) mol/L but decreased significantly at 10(-7) mol/L in arterioles of eNOS-KO compared with those of WT mice. These findings demonstrate that, despite the lack of nitric oxide mediation, flow-induced dilation is close to normal in arterioles of eNOS-KO mice because of an enhanced release of endothelial dilator prostaglandins and suggest that this vascular adaptation may contribute to the regulation of peripheral resistance in eNOS-KO mice.

Topics: Animals; Arterioles; Blood Circulation; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Epoprostenol; In Vitro Techniques; Indomethacin; Male; Mice; Mice, Knockout; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Nitroarginine; Prostaglandins; Vasodilation

This study was conducted to determine if high perinatal prostaglandin (PG) and thromboxane (TxA2) levels modified their choroidal vasomotor effects and receptor levels. Both nonperfused (eyecup preparations) and perfused choroidal vessels from saline- or ibuprofen-treated 1-day-old pigs and tissues from adult pigs were used; all prostanoids produced similar vasomotor effects on both preparations. Choroidal PGF2alpha, TxA2, PGI2, and PGD2 levels were higher in the newborn than in adult pigs; injections of ibuprofen (40 mg/kg every 4 h for 48 h) into newborn pigs significantly decreased choroidal levels of all these prostanoids. PGF2alpha and the TxA2 mimetic U-46619 caused less choroidal vasoconstriction and production of inositol 1,4,5-trisphosphate (IP3) in the newborn than in adult pigs. Ibuprofen treatment increased choroidal PGF2alpha vasoconstrictor effects, IP3 production, and receptors, but did not modify response to U-46619. Carbaprostacyclin (PGI2 analog) caused a greater choroidal vasodilatation and adenosine adenosine 3',5'-cyclic monophosphate (cAMP) production in the newborn than in adult pigs; these effects were not modified by ibuprofen. PGD2 did not increase cAMP but caused greater dilatation and nitrite [oxidation product of nitric oxide (NO)] production in the choroid of newborn than of adult pigs, which were decreased to adult levels by ibuprofen and the NO synthase inhibitor N(omega)-nitro-L-arginine. These data suggest that high perinatal PG levels downregulate PGF2alpha receptors and vascular effects but do not modify choroidal responses to TxA2 and PGI2; NO seems to contribute to the vasodilator effects of PGD2.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Aging; Animals; Animals, Newborn; Choroid; Cyclic AMP; Cyclic GMP; Dinoprost; Down-Regulation; Epoprostenol; Ibuprofen; Inositol 1,4,5-Trisphosphate; Nitric Oxide; Nitroarginine; Prostaglandin D2; Prostaglandin Endoperoxides, Synthetic; Prostaglandins; Prostaglandins, Synthetic; Receptors, Prostaglandin; Swine; Thromboxane A2; Vasoconstrictor Agents; Vasodilation