Genetic aberrations in cation homeostasis appear to be involved in the etiology of essential hypertension. Homegeneous populations of vascular smooth muscle cells (SMC) will be obtained by cell culture methods from the thoracic aorta of normotensive and hypertensive rat strains including the Okamoto spontaneously hypertensive and Wistar-Kyoto control strains as well as the Dahl R and S strains. The cellular concentrations of Na+, K+, and free cytoplasmic Ca++ will be measured. The amount per cell of the calcium regulator protein, calmodulin, will be determined by radioimmunoassay and biological activity. The specific activities of three separate Na+ transport systems will be measured: 1) amiloride-inhibitable Na+ influx; 2) furosemide-inhibitable Na+, K+, Cl- cotransport; and 3) Na+ pump activity. They will be assayed as a function of external Na+ in the case of the Dahl R and S rats. Angiotensin II (AII) stimulates Na+ influx in cultured vascular SMC and isolated aortic tissue. Amiloride prevents AII from increasing Na+ influx. The stimulatory effect of AII on amiloride-inhibitable Na+ influx by SMC cultured from the normotensive and hypertensive strains will be compared. The proliferative response of quiescent SMC to growth-promoting hormones will be compared. These investigations will test the hypothesis that a membrane defect in cation transport in the SMC is a primary factor in the etiology of genetic hypertension. Cell culture offers the possibility of establishing cell lines for identifying the genetically predisposing lesions in hypertension.
