John W Seawright1, Andreea Trache2,3, Emily Wilson2, Christopher R Woodman4,5. 1. Department of Health and Kinesiology, MS 4243, Texas A&M University, College Station, TX, 77843-4243, USA. 2. Department of Medical Physiology, Texas A&M University, College Station, TX, USA. 3. Department of Biomedical Engineering, Texas A&M University, College Station, TX, USA. 4. Department of Health and Kinesiology, MS 4243, Texas A&M University, College Station, TX, 77843-4243, USA. woodmanc@hlkn.tamu.edu. 5. Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA. woodmanc@hlkn.tamu.edu.
Abstract
PURPOSE: We tested the hypothesis that exposure to a short-duration (1 h) increase in intraluminal pressure, to mimic pressure associated with a bout of exercise, would attenuate age-induced impairments of vascular smooth muscle (VSM) constrictor responses in soleus muscle feed arteries (SFA) via the Rho pathway. METHODS: SFA from young (4 months) and old (24 months) Fischer 344 rats were cannulated and pressurized to 90 or 130 cmH2O for 1 h. Following the 1-h treatment, pressure in P130 arteries was lowered to 90 cmH2O for examination of vasoconstrictor responses to norepinephrine (NE), angiotensin II (Ang II), and phenylephrine (PE). To assess the role of the Rho pathway, vasoconstrictor responses were assessed in the absence or presence of a RhoA-kinase inhibitor (Y27632) or RhoA-kinase activator (LPA). RESULTS: Vasoconstrictor responses to NE, Ang II, and PE were impaired in old P90 SFA. Pretreatment of old SFA with increased pressure improved vasoconstrictor responses to NE, PE and Ang II. The beneficial effect of the pressure pretreatment in old SFA was eliminated in the presence of Y27632. In the presence of LPA, vasoconstrictor responses to Ang II were improved in old SFA such that responses were not different than young P90 SFA. CONCLUSION: These results indicate that a short-duration exposure to increased intraluminal pressure, to mimic pressure associated with a bout of exercise, attenuates or reverses the age-related decrement in VSM constrictor responses in SFA and that the beneficial response is mediated through Rho kinase.
PURPOSE: We tested the hypothesis that exposure to a short-duration (1 h) increase in intraluminal pressure, to mimic pressure associated with a bout of exercise, would attenuate age-induced impairments of vascular smooth muscle (VSM) constrictor responses in soleus muscle feed arteries (SFA) via the Rho pathway. METHODS: SFA from young (4 months) and old (24 months) Fischer 344 rats were cannulated and pressurized to 90 or 130 cmH2O for 1 h. Following the 1-h treatment, pressure in P130 arteries was lowered to 90 cmH2O for examination of vasoconstrictor responses to norepinephrine (NE), angiotensin II (Ang II), and phenylephrine (PE). To assess the role of the Rho pathway, vasoconstrictor responses were assessed in the absence or presence of a RhoA-kinase inhibitor (Y27632) or RhoA-kinase activator (LPA). RESULTS: Vasoconstrictor responses to NE, Ang II, and PE were impaired in old P90 SFA. Pretreatment of old SFA with increased pressure improved vasoconstrictor responses to NE, PE and Ang II. The beneficial effect of the pressure pretreatment in old SFA was eliminated in the presence of Y27632. In the presence of LPA, vasoconstrictor responses to Ang II were improved in old SFA such that responses were not different than young P90 SFA. CONCLUSION: These results indicate that a short-duration exposure to increased intraluminal pressure, to mimic pressure associated with a bout of exercise, attenuates or reverses the age-related decrement in VSM constrictor responses in SFA and that the beneficial response is mediated through Rho kinase.
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