Ouabain increases vascular resistance and may induce hypertension by inhibiting the Na + pump. The effects of 0.18 and 18 µg/kg, and 1.8 mg/ kg ouabain pretreatment on the phenylephrine (PHE; 0.1, 0.25 and 0.5 µg, in bolus)-evoked pressor responses were investigated using anesthetized normotensive (control and uninephrectomized) and hypertensive (1K1C and DOCA-salt treated) rats. Treatment with 18 µg/kg ouabain increased systolic and diastolic blood pressure in all groups studied. However, the magnitude of this increase was larger for the hypertensive 1K1C and DOCA-salt rats than for normotensive animals, while the pressor effect of 0.18 µg/kg ouabain was greater only in DOCA-salt rats. A very large dose (1.8 mg/kg) produced toxic effects on the normotensive control but not on uninephrectomized or 1K1C rats. Rat tail vascular beds were perfused to analyze the effects of 10 nM ouabain on the pressor response to PHE. In all animals, 10 nM ouabain increased the PHE pressor response, but this increase was larger in hypertensive DOCA-salt rats than in normotensive and 1K1C rats. Results suggested that a) increases in diastolic blood pressure induced by 18 µg/kg ouabain were larger in hypertensive than normotensive rats; b) in DOCA-salt rats, smaller ouabain doses had a stronger effect than in other groups; c) hypertensive and uninephrectomized rats were less sensitive to toxic doses of ouabain, and d) after treatment with 10 nM ouabain isolated tail vascular beds from DOCA-salt rats were more sensitive to the pressor effect of PHE than those from normotensive and 1K1C hypertensive rats. These data suggest that very small doses of ouabain, which might produce nanomolar plasma concentrations, enhance pressor reactivity in DOCA-salt hypertensive rats, supporting the idea that endogenous ouabain may contribute to the increase and maintenance of vascular tone in hypertension. Correspondence

These finding suggest that at 3 days after MI the iNOS modulates the isolated papillary muscle response to isoprenaline and its inhibition improves the beta-adrenergic inotropic responses.

The acute phase of myocardial infarction promotes an inflammatory response that stimulates inducible nitric oxide synthase (iNOS). We investigated the iNOS role on the rat tail vascular bed reactivity 3 days after myocardial infarction. Vasodilator and vasoconstrictor responses were determined in isolated caudal vascular beds from Wistar rats 3 days after coronary artery ligation (CAL) and sham-operated animals (SHAM). Rats were treated with the iNOS inhibitor S-methylisothiourea sulfate (SMT), 5 mg Kg day, i.p. or placebo. Concentration of plasma nitrite/nitrate (NOx) and the expression of iNOS mRNA in tail arteries were evaluated. The CAL group showed increased maximal vasoconstrictor response to phenylephrine (SHAM= 241 +/- 8; CAL= 288 +/- 13 mm Hg, P < 0.05) and SMT treatment normalized this effect (CAL-SMT = 253 +/- 7 mm Hg, P < 0.05). The sensitivity to acetylcholine was reduced in the CAL group, but SMT treatment did not alter this response. The plasma NOx and iNOS mRNA expression in tail arteries were increased in CAL rats. SMT treatment reduced the plasma NOx in the CAL group and the arterial expression of iNOS mRNA in SHAM and CAL group. In conclusion, iNOS inhibition prevented the increased phenylephrine reactivity in rat caudal vascular beds 3 days after myocardial infarction.

The increase in right ventricular systolic pressure observed in vivo after the administration of mercury opposes to the idea that the metal depresses the cardiac pump performance. We then investigated the effects of HgCl(2) (0.1 to 2.5 microM) on the contractile activity of the right ventricular myocardium, measuring isometric and tetanic contractions of right ventricular isolated strips, right ventricular isovolumic systolic and diastolic pressures, and the coronary perfusion pressure (0.03 to 3 microM) in constant-flow Langendorff-perfused rat hearts. The results presented here suggest that the acute effects of mercury on the right ventricular myocardium are distinct. When isolated strips of right ventricular wall are used, the contractile depression produced by mercury is manifested. However, when mercury is administered to isolated perfused hearts or in vivo this depressant effect is not revealed. The possible reasons for this behavior are the increased coronary perfusion pressure, which promotes a positive inotropic effect, manifested during the infusion of increasing concentrations of mercury, or the putative stretch of the ventricular fibers, which might cause the increment of diastolic pressure. An interesting finding is that the mechanical activity of the preparations, in which mercury is administered via coronary circulation, is not depressed and, even more, it can increase systolic pressure. However, the nature of this protective effect of coronary circulation cannot be explained by the results presented here.