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Calcium uptake and efflux were studied in aortic tissues of three inbred rat strains; spontaneously hypertensive rats (SHR), inbred Dahl salt-sensitive rats (S/JR) and inbred Dahl salt-resistant (R/JR) rats. Previously, we showed that a single genetic locus (Hyp-2 locus) controls vascular smooth muscle responses to ionic cobalt (Co2+) among these three strains . Spontaneously hypertensive rats carry an allele at the Hyp-2 locus mediating high blood pressure, but S/JR and R/JR both carry an allele at this locus for low blood pressure. In the present work, resting Ca2+ uptake in aortic tissue was found to be increased in SHR and S/JR relative to R/JR. It was concluded that resting aortic Ca2+ uptake and genotypes at the Hyp-2 locus are not concordant among strains and that the increased Ca2+ uptake of the hypertensive strains must, therefore, be mediated by a mechanism other than the Hyp-2 locus. Resting aortic Ca2+ uptake was shown also to be increased in hypertension-resistant R/JR rats by the extreme treatment of unilateral nephrectomy plus 8% NaCI diet which induces hypertension in R/JR rats. The high resting vascular smooth muscle calcium-uptake seen in the hypertensive strains is, therefore, not a unique primary genetic cause of hypertension since it can also be induced by environmental manipulation. High resting aortic Ca2+ uptake is either a consequence of hypertension or a final common physiological pathway by which genetic and environmental factors influence blood pressure.