Electrical and mechanical responses of rat middle cerebral arteries to reduced P O 2 and prostacyclin

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.

High-salt diet impairs vascular relaxation mechanisms in rat middle cerebral arteries

“…Arteries from rats maintained on either a short-term or a chronic low-salt diet dilated in response to reduced PO 2 and iloprost, as previously reported for MCA of animals on a normal salt diet (7,20). However, arteries of rats maintained on the high-salt diet for either 3 days or for 4-8 wk exhibited a paradoxical constriction in response to both reduced PO 2 and iloprost.…”

“…In some experiments, we tested the effect of endothelial removal on the response of the vessels to reduced PO2 and iloprost. In those studies, the endothelium was removed by air bolus perfusion, as previously described (7,20). The presence or absence of intact endothelial function was evaluated by determining the response of the vessels to 1 M acetylcholine before and after air perfusion.…”

“…In another series of experiments, VSM transmembrane potentials (Em) were measured with a high-impedance amplifier and glass microelectrodes (40-80 M⍀ impedance) filled with 3 M KCl, as previously described (6,7,18,20,37). Criteria for a successful impalement included an abrupt drop to a steady level of E m for a minimum of 5 s and an abrupt return to baseline on exit of the electrode from the cell.…”

“…Previous studies by our group (7,20) have indicated that endothelium-derived cyclooxygenase (COX) metabolites, most likely prostacyclin, mediate hypoxic dilation in response to reduced PO 2 in rat MCA. Several other studies (1,28,34) have suggested that a COX product, most likely prostaglandin H 2 (PGH2) or thromboxane A2 (TxA2), acts as a constrictor factor in several forms of hypertension.…”

“…In an additional series of experiments, we assessed the production of prostacyclin I 2 (PGI2) and TxA2 by cerebral arteries during exposure to reduced PO 2, as described previously (20). In those studies, brains were removed from anesthetized rats that were on either low-salt or high-salt diet for 1 wk.…”