Project Summary Olfactory Receptors (ORs) comprise the largest gene family in the genome, and ORs serve key functions in a variety of tissues beyond the nose. We have identified an evolutionarily conserved OR, Olfr558, which localizes to vascular smooth muscle cells and plays a role in blood pressure regulation. It is well-established, in both humans and in animal models, that normotensive premenopausal females have lower blood pressure than normotensive males by approximately ~10mmHg. In contrast, blood pressure is similar in postmenopausal females and males, due to an increase in female blood pressure with aging. We find that sex differences in blood pressure are absent in Olfr558 knockout (KO) mice, and, that wild-type (WT) but not KO females increase blood pressure with aging. In this proposal, we will explore the role of Olfr558 in mediating changes in blood pressure in aging. In Aim 1, we will compare blood pressure by telemetry between WT and KO mice which are young (4-7 months, male and female), aged (18-22 months, male and female), or young (4-7 months) females in whom menopause has been chemically induced via VCD (4-vinylcyclohexene diepoxide). In Aim 2, we will use tissues from these same mice to assay how renin (Aim 2a) and vascular reactivity (Aim 2b) are altered in WT vs KO in these various groups. These studies will uncover the role of a well-conserved OR in the cardiovascular physiology of aging, and in so doing will reveal novel insights into sex differences, blood pressure regulation, aging, and menopause.