Isolated resistance arteries from the gracilis muscle of rats were simultaneously perfused and superfused with physiological salt solution (PSS) equilibrated with control (21% O2) and reduced (15, 10, 5, or 0% O2) concentrations of O2. The vessels exhibited a significant dilation in response to reduced PO2, which could be inhibited by selective perfusion of the lumen with 21% O2 PSS, endothelial removal, and 1 microM indomethacin, but was unaffected by the nitric oxide synthase inhibitor N omega-nitro-L-arginine (10 microM). Contraction of the arteries in response to 50 mM K+ was inhibited by 0% O2, whereas agonist (norepinephrine and serotonin)-induced contractions and pressure-induced myogenic responses were insensitive to reduced PO2. These results suggest that 1) skeletal muscle resistance arteries are intrinsically sensitive to reduced PO2 independent of parenchymal cell influences, 2) inhibition of resting tone in these vessels is mediated by an endothelium-derived product of the cyclooxygenase pathway, and 3) various forms of contractile activation are not equally sensitive to inhibition by reduced PO2 in extraparenchymal resistance arteries of skeletal muscle.

No abstract

Isolated rat middle cerebral arteries were perfused and superfused with physiological salt solution equilibrated with a control (∼140 mmHg) or reduced (∼35–40 mmHg)[Formula: see text]. In other experiments, cerebral arteries were isolated and prostacyclin release was determined by radioimmunoassay for 6-ketoprostaglandin F1α. Equilibration of the vessels with reduced[Formula: see text] (35 mmHg) solution caused a significant increase in prostacyclin release relative to control[Formula: see text] (140 mmHg) conditions. Exposure of middle cerebral arteries to reduced[Formula: see text] caused vascular smooth muscle (VSM) hyperpolarization and vessel relaxation, which could be blocked by 1 μM glibenclamide, an inhibitor of the ATP-sensitive K+ channel, but not by 1 mM tetraethylammonium (TEA), an inhibitor of the Ca2+-activated K+ channel. Glibenclamide also inhibited VSM hyperpolarization and vasodilation in response to the stable prostacyclin analog iloprost, but TEA did not affect iloprost-induced dilation of the vessel. Endothelial removal eliminated the electrical and mechanical responses of the arteries to reduced[Formula: see text], but vessel responses to iloprost were similar to those of intact vessels. The results of this study are consistent with the hypothesis that hypoxic dilation of rat middle cerebral arteries is due to VSM hyperpolarization mediated by prostacyclin-induced activation of glibenclamide-sensitive K+ channels.

This study assessed vasodilator responses in skeletal muscle resistance arteries (100-250 microns) from rats with chronic (4-8 wk) reduced renal mass (RRM) hypertension and normotensive sham-operated controls on a high (4% NaCl; HSSHAM)- or low (0.4% NaCl; LSSHAM)-salt diet. Arteries from RRM hypertensive rats [normal and high-salt diet (HSRRM)] and a separate group of spontaneously hypertensive rats exhibited an impaired dilation in response to reduced PO2 compared with those of their normotensive controls. Prostacyclin release, assessed by radio-immunoassay for 6-ketoprostaglandin F1 alpha, increased significantly in response to reduced PO2, but was unaffected by hypertension or salt intake. Dilator responses to acetylcholine and the prostacyclin analog iloprost were significantly reduced in both HSRRM and HSSHAM compared with LSSHAM rats. Dilation in response to direct activation of adenylate cyclase with forskolin or guanylate cyclase with the nitric oxide donor sodium nitroprusside was not significantly different in HSRRM, HSSHAM, and LSSHAM rats. These results indicate that hypoxic dilation is impaired in skeletal muscle resistance arteries of hypertensive rats and that chronic high-salt diet alone leads to impaired vasodilator responses in resistance arteries of normotensive animals, possibly via abnormalities in membrane function or G protein signaling rather than impaired second-messenger function.

Isolated middle cerebral arteries of rats were perfused and superfused simultaneously with physiological salt solution (PSS) equilibrated with control (21% O2) or with reduced O2 concentrations (15, 10, 5, or 0% O2). Arterial dilation in response to reduced PO2 was unaffected by the nitric oxide synthase inhibitor N omega-nitro-L-arginine (10 microM) but was inhibited by selective perfusion of the lumen with 21% O2 PSS (0% O2 in the superfusion), endothelial removal, and 1 microM indomethacin. Arterial dilation during reduced PO2 was unaffected by 1 mM tetraethylammonium to block the Ca(2+)-dependent "maxi-K+" channel but was eliminated by 1 microM glibenclamide, a blocker of the ATP-sensitive K+ channel. Glibenclamide also inhibited dilation of the vessels in response to the stable prostacyclin analogue, iloprost. The results of this study suggest that dilation of rat middle cerebral arteries in response to reduced PO2 is mediated by an endothelium-dependent cyclooxygenase product, which activates glibenclamide-sensitive K+ channels.