CALCIUM, PHOSPHOINOSITIDE, AND 1,2-DIACYLGLYCEROL RESPONSES OF BLOOD-VESSELS OF DEOXYCORTICOSTERONE ACETATE SALT HYPERTENSIVE RATS TO ENDOTHELIN-1

In previous studies a decreased responsiveness to endothelin-1 (ET-1) of conduit arteries and resistance vessels of deoxycorticosterone acetate (DOCA)-salt hypertensive rats was found in comparison with uninephrectomized controls. Decreased isometric force, number of receptors, and inositol phosphate accumulation were reported in the DOCA-salt animals. In the present study effects of ET-1 on cytosolic free calcium, inositol phosphates, and 1,2-diacylglycerol were investigated in blood vessels of DOCA-salt hypertensive rats. Basal cytosolic free calcium, measured with the fluorescent dye fura-2, was 201+/-41 nmol/l in mesenteric arteries of DOCA-salt rats and 45+/-9 nmol/l in uninephrectomized controls (p<0.01). The maximal response of cytosolic free calcium (to 30 nmol/l ET-1) was 176+/-22% of the basal value for DOCA-salt and 242+/-6% for uninephrectomized rats (p<0.05). The concentration giving 50% of the maximum response was 9.0 and 6.5 nmol/l for DOCA-salt rats and controls, respectively. Inositol phosphate production after stimulation with 100 nmol/l ET-1 in the presence of LiCl was lower by at least 30% (p<0.01) in both aorta and mesenteric arteries of DOCA-salt hypertensive versus control rats. Basal levels of diacylglycerol in aorta were similar in DOCA-salt rats and in controls and did not respond to a 100 nmol/l ET-1 stimulation in the DOCA-salt rats, in contrast to the increase found in the control uninephrectomized rats (p<0.05). Thus, the diminished response to ET-1 of DOCA-salt rat arteries may be due to a lower density of ET-1 receptors, resulting in a blunted signal transduction, as reflected by decreased responses of inositol phosphate, cytosolic free calcium, and diacylglycerol.