INTRACELLULAR CALCIUM-CONCENTRATION IN VASCULAR SMOOTH-MUSCLE CELLS OF RATS WITH CIRRHOSIS

A decreased presser response to endogenous vasoconstrictors, such as angiotensin II and vasopressin, is a characteristic finding in cirrhosis with ascites; this has been considered as partially responsible for the arteriolar vasodilation present in this disease. Previous investigations suggested that this abnormality is due to a post-receptor defect leading to altered intracellular Ca2+ mobilization. To assess this hypothesis, vascular responsiveness to angiotensin II (3.10(-8) M) and intracellular Ca2+ concentration in basal conditions and following angiotensin II (1-100 nM) and vasopressin stimulation (100 nM) were measured in aortic rings and in primary cultured aortic vascular smooth muscle cells, respectively. The study was carried out in 43 control rats and 40 rats with CCl4-induced cirrhosis and ascites. Cells were grown to confluence on glass cover slips and then loaded with Fura-2, a fluorescent intracellular Ca2+ indicator, for continuous monitoring of intracellular Ca2+ concentration. A decreased constrictor response to angiotensin II was detected in cirrhotic aortic rings in comparison to control rings (increase in tension: 31+/-5 vs 79+/-14 mg, p<0.005). No differences in intracellular Ca2+ concentration between cirrhotic and control cells were observed in basal conditions (104+/-6 and 100+/-3 nM, respectively). Angiotensin II administration to cirrhotic vascular smooth muscle cells had a dose-dependent biphasic effect consisting of a rapid increase, followed by return to a sustained level significantly higher than the basal value. This response was identical to that observed in control vascular smooth muscle cells. Similar findings were obtained following vasopressin stimulation. These results indicate that although isolated aorta from animals with ascites and cirrhosis have hyporesponsiveness to angiotensin II, the intracellular Ca2+ mobilization pathway is preserved in the vascular smooth muscle cells of these rats, arguing against the post-receptor defect hypothesis of impaired responsiveness to vasoconstrictors in cirrhosis. (C) Journal of Hepatology.