Altered endothelin-dependent regulation of blood pressure and vascular tone in stress-sensitive august rats

The endothelin (ET) system was studied in August rats, with genetically determined high sensitivity to stress, and in control Wistar rats. Radioimmunoassay revealed a significant difference in plasma endothelin-1 (ET-1) levels of August vs Wistar rats (7.1 fmol/ml vs 50.0 fmol/ml). Immobilization of the animals increased these values up to 11.0 fmol/ml and 65.2 fmol/ml, respectively. Elevation of ET-1 was associated with an increase in blood pressure, which was similar in both strains, whereas the heart rate increase was diminished in the stress-sensitive rats. The mixed endothelin-A/endothelin-B- (ET(A)/ET(B)) receptor antagonist PD142893 suppressed stress-induced elevation of blood pressure in August, but not in Wistar rats. In both strains, heart rate responses to stress were insensitive to the ET receptor blockade. Aortic rings of August rats displayed diminished sensitivity to the vasoconstrictor action of ET-1 vs that of Wistar rats (EC50 = 22.1 nM vs 6.3 nM, respectively). In noradrenaline-precontracted tail arteries, 50 nM ET-1 elicited further constriction without any vasodilator effects. ET-1-induced increase in perfusion pressure was greater in tail arteries of Wistar rats. Thus, endogenous ET-1 can play a strain-dependent role in the stress-induced responses of haemodynamics and the alterations in endothelin-dependent regulation may be responsible for the differences in vascular reactivity of Wistar and August rats.