The relaxation induced by S-nitroso-glutathione and S-nitroso-N-acetylcysteine in rat aorta is not related to nitric oxide production.

S-nitroso-glutathione (GSNO) and S-nitroso-N-acetylcysteine (NACysNO) are nitrosothiols that release nitric oxide (NO) and mimic the effects of endogenous NO. This study investigated the relaxation induced by GSNO and NACysNO in rat aorta and the relation between relaxation and NO formation. Both compounds at concentrations from 10(-9) M to 10(-4) M relaxed the rat aorta in a concentration-dependent manner. However, NO production depended on the concentration of nitrosothiols present and was detected only above 100 microM GSNO or NACysNO. To determine whether K+ channels are involved in the relaxation induced by nitrosothiols, the contractions were induced with KCl at concentrations of 30, 60, or 90 mM. The concentration-effect curves for the relaxation induced by nitrosothiols were shifted to the right for all the K+ concentrations compared with aortas precontracted with phenylephrine. These results indicate the participation of K+ channels in the relaxation induced by GSNO and NACysNO. A selective inhibitor of soluble guanylyl cyclase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, significantly inhibited the relaxation induced by the nitrosothiols. The relaxation induced by GSNO and NACysNO was inhibited by the K+ channel blockers glibenclamide, selective K(ATP) channels, and apamin, selective for low-conductance Ca2+-activated K+ channels in rat aorta, but was not inhibited by charybdotoxin, a potent and selective Ca2+-activated K+ channel blocker, or by 4-aminopyridine, a voltage-gated K+ channel blocker. These results indicate that relaxation induced by GSNO and NACysNO is partially due to activation of K(ATP) channels and partially due to activation of low-conductance Ca2+-activated K+ channels. However, the ability of the nitrosothiol compounds to overcome the inhibitory effect of high extracellular K+ concentrations suggests another mechanism of relaxation contributing to the nitrosothiol response. The most intriguing finding is that relaxation is not related to the NO produced in rat aorta.

Alterations of calcium uptake in renovascular hypertensive rat aorta: functional assessment with thapsigargin.

1. The aim of this study was to test the hypothesis that impaired calcium (Ca2+) recycling by sarcoplasmic reticulum (SR) Ca2+-ATPase takes place in aortae from 1 kidney-1 clip (1K-1C) hypertensive rats. 2. The contractile response elicited when Ca2+ is released from the SR with phenylephrine and caffeine in Ca2+-free Krebs solution was greater in 1K-1C than in 1K rat aorta. In the arteries submitted to intracellular Ca2+ store depletion and reloading, this response was not different between 1K-1C and 1K rat aortae. Thapsigargin decreased the phasic contractile responses to phenylephrine in 1K and 1K-1C rat aortae and increased the tone that developed during the refilling period in 1K-1C rat aortae. 3. Our data support the hypothesis that the 1K-1C rat aorta has defective intracellular Ca2+ regulation that may be implicated in an inadequate SR buffering ability.

Increased contractile response induced with ouabain is abolished by thapsigargin in aorta of renal hypertensive rats.

1. The aim of the present study was to test in vitro if the increased contractile effect of phenylephrine and KCl, observed after the addition of ouabain in renal hypertensive rat aorta, is mediated by Ca2+ accumulated on the sarcoplasmic reticulum. 2. In aortas of one kidney (1K) rats, ouabain did not modify the concentration-effect curves stimulated with phenylephrine and KCl. 3. Contractile responses stimulated with phenylephrine and KCl were potentiated by ouabain in one kidney--one clip (1K-1C) aortas, and preincubation with thapsigargin abolished the increasing effect of ouabain on these contractions. 4. The addition of thapsigargin before phenylephrine and KCl did not modify the contractile response to phenylephrine and KCl or the resting vascular tone during the time incubation. 5. In the presence of ouabain, thapsigargin significantly increased the vascular tone only in 1K-1C rat aortas. 6. Increased intracellular Na+ concentration as a consequence of Na(+)-K(+)-ATPase inhibition induces increased accumulation of Ca2+ inside the sarcoplasmic reticulum in 1K-1C rat aortas. The differential effects in renal hypertensive and normotensive aortas suggest a possible role of this mechanism in modulating cytosolic Ca2+ in renal hypertension.