Effect of Olvanil (TRPV1 agonist) on the blood pressure response to treadmill exercise in rats with simulated peripheral artery disease

Peripheral artery disease (PAD) is a common and debilitating ischemic vascular disease primarily impacting the lower limbs. Individuals with PAD experience an exaggerated blood pressure (BP) response to physical activity/exercise that increases the risk of severe cardiac events and death. Capsaicin, a TRPV1 receptor agonist, has been shown to reduce the BP response to exercise in rat models of PAD. However, capsaicin’s noxious properties create the need for an alternative approach to translate those findings to potential therapies. Olvanil is a non-noxious capsaicin analogue that may be capable of reducing the BP response to exercise, but this possibility has not been investigated. Objective and hypothesis: We tested the hypothesis that intravenous infusion of Olvanil (2 mg) would reduce the BP response to treadmill exercise in a rat model of simulated PAD in which both femoral arteries were ligated for 72 hours. Methods: Sprague-Dawley rats (n=11, 5M/6F, ~12 weeks old) had both femoral arteries surgically ligated ~72 hours prior to experiments. On experiment day, the right carotid artery and jugular vein were cannulated (PE-50) for BP measurement and Olvanil administration, respectively. After recovery from surgery (at least 2 hrs), rats completed a control 4 min treadmill exercise bout (15 m/min, 1° incline) while BP was continuously recorded. Arterial blood samples were collected just prior to the end of exercise for blood glucose and lactate measurement. 10 min later, Olvanil (2mg) was infused into the jugular vein. 15 min after infusion, a second treadmill exercise bout was performed. The BP response to exercise before (control) and after Olvanil infusion were disaggregated by sex and compared between conditions. Data are mean±SEM. Results: In male rats, Olvanil had no effect on the peak mean arterial pressure response (peak DMAP) to exercise (control: 22±1, Olvanil: 22±1 mmHg, P=0.913). In female rats, Olvanil significantly reduced the peak DMAP response to exercise (control: 21±1, Olvanil: 14±1 mmHg, P=0.020). Olvanil significantly increased exercising blood glucose in male (control: 126±7, Olvanil: 150±8 mg/dl, P=0.001) and female (control: 127±7, Olvanil: 169±14 mg/dl, p=0.006) rats. Olvanil, significantly increased exercising blood lactate in female rats (control: 1.7±0.1, Olvanil: 2.3±0.3 mmol/L, P=0.050), but not male rats (control: 1.4±0.3, Olvanil: 1.4±0.2 mmol/L, P >0.822). Conclusion: Olvanil attenuated the BP response to treadmill exercise in female but not male rats with simulated PAD which may have implications for reducing cardiovascular risk in PAD patients. However, further work is needed to understand the concurrent effect of systemic Olvanil administration on glycemic and metabolic regulation.National Institutes of Health R01HL161160 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.