In this study, we demonstrated similar findings in WKY and in SHR as already reported, indicating that hypertension did not affect the ATR expression patterns with age. A marked reduction of Ang IIinduced contraction in only 40-week SHR aortic rings with blocking of the AT2R-related signaling pathways provided further information that reduced AT1R-contraction in aged SHR would Gomisin-D result from any reduction of AT1R-related signaling cascade by hypertension regardless of enhanced AT1R expression with age. A similar spectrum was also obtained in aged Fisher 344 rats and in SHR. Alternatively, as Arun et al. reported, altered i incorporation through reduction in the AT1R-coupled VDCC phosphorylation pathway may be involved in the reduced contraction by Ang II in aged SHR. Contrary to this finding, as Davare and Hell revealed that aging caused increased phosphorylation of VDCC in neuronal network system of the brains. Thus, further experiments regarding VDCC phosphorylation in rats are needed to clarify whether aging alters Ca2+ sensitivity via aortic VDCC. In the present study, we demonstrated that aging reduced contraction responsiveness at initial phase to VDCC agonist, Bay K 8644, for both WKY and SHR, although tensions at plateau contraction phase were unaltered between young and aged rats as similar to the result by Hernandez et al.. The slower responsiveness to Bay K 8644 at initial contraction phase in aged rats would be caused by reduced activation of VDCC or reduced VDCC expression with age. In this study, we demonstrated that aging reduced the aortic L-type VDCC protein expression in rats for the first time. Similar findings have been reported for sinoatrial node and for cerebral artery. However, it still remains unclear whether aging may affect the expression of other Ca2+ channel subtypes such as R- and T-type, located in the heart and in the kidney. As speculated from the reduced VDCC expression in aged rats, the attenuated relaxation activity of VDCC blockers occurred in PE-contraction aortic rings. In contrast, no change in the potent relaxation activity of nifedipine, another type of VDCC blocker, between young and aged SHR was found irrespective to their different VDCC expressions. This might be explained by alternative roles of nifedipine in vasorelaxation signaling pathways by activating AMP-activated protein kinase and endothelial NO synthase. However, further study on the relationship between activation of relaxationsignaling pathways by VDCC blockers and aging is needed. The disappearance of the relaxation 6-gingerol potential of Trp-His in aged rats also provided useful information suggesting that bioactive natural compounds having preventive health-benefits for vascular disease via VDCC blocking action may fail to evoke the preventive potential with aging. In conclusion, we have clarified that aging greatly attenuated the PE- and Ang II-induced contractions in SHR, whereas WKY did not loss the contraction responses. Together with the results on enhanced AT1R and reduced AT2R in both aged WKY and SHR, we demonstrated for the first time that L-type VDCC protein expression was greatly reduced with age in rats.