Abstract Body: We previously identified olfactory receptor 558 (Olfr558) expression in kidney renin-producing cells and vascular smooth muscle (PMID: 38507492). Although sex-based differences in normotensive blood pressure (BP)— lower in females—are well documented, we found these differences absent in Olfr558 knockout (KO) mice for systolic (SBP), diastolic (DBP), and mean arterial pressure (MAP). In early adulthood (3–4 months), male KOs exhibited diminished renal renin and Akr1b7 transcript levels along with reduced plasma renin activity (PRA) compared to wildtype (WT) males, whereas female KOs demonstrated increased pulse wave velocity (PWV) relative to WT females. Here, we investigated whether these differences persist or evolve with age, as sex differences in BP commonly attenuate over time.
Blood pressure was monitored via telemetry, while renal gene expression of Olfr558, renin, and Akr1b7 was assessed by qPCR (delta Ct, arbitrary units). PRA was measured by ELISA, and aortic stiffness was evaluated through PWV. Older WT females (12–13 months, n=8) displayed significantly elevated MAP (105.9±1.1 vs. 93.2±1 mmHg), SBP (118.4±1.2 vs. 106.9±1 mmHg), and DBP (93.7±1 vs. 78.8±1 mmHg) compared to younger WT females (5–6 months, n=8; all p<0.0001). In contrast, age-related BP increases were not observed in KO females: MAP (98.9±1.2 vs. 98.3±1.4 mmHg), SBP (112.3±1.3 vs. 112.2±1.4 mmHg), and DBP (85.1±1 vs. 84.0±1.2 mmHg). Among aged males (15–21 months), KOs (n=5) and WTs (n=4) exhibited comparable levels of renin (1.4±0.1 vs. 1.4±0.2 a.u.), Akr1b7 (0.07±0.004 vs. 0.08±0.006 a.u.), and PRA (158±17 vs. 211±60 ng Ang-1/mL/hr). However, aged KO females (n=5) continued to show significantly elevated PWV versus both aged WT females (n=6) and KO males (7.2±0.1 vs. 4.9±0.5 and 5.0±0.7 m/s, p<0.05). Renal Olfr558 expression was higher in young WT females (4 months, n=8–9) than in males (0.011±0.0007 vs. 0.007±0.0004 a.u., p<0.05), with a more pronounced sex gap in older mice (15–21 months, n=4–5; 0.016±0.0015 vs. 0.007±0.0004 a.u., p<0.0001). Similarly, cardiac Olfr558 expression was greater in young WT females (0.0001±3.25×10^-6 vs. 0.0001±0.00001 a.u., p<0.01) and remained elevated in older females (0.00009±0.000004 vs. 0.00007±0.000002 a.u., p<0.05) despite overall age-related reductions. Collectively, these data indicate that Olfr558 may play a key role in the age-associated rise in BP, particularly in females post-reproductive age.