The modulatory role of myogenic tone on alpha-1 adrenergic-mediated cerebral vasomotor responses

Myogenic reactivity and alpha-1 adrenergic signalling contribute to the regulation of cerebrovascular tone. Whether the level of myogenic tone influences alpha-1 adrenergic signalling in the cerebral circulation is unclear. Therefore, the purpose of the present study was to explore whether myogenic tone influences alpha-1 adrenergic-mediated vasoconstriction in isolated cerebral arteries. It was hypothesized that myogenic tone and alpha-1 adrenergic-mediated vasoconstriction would act synergistically to enhance cerebral artery tone (i.e., arteries with higher myogenic tone would display the greatest constriction to alpha-1 adrenergic agonism). Middle cerebral arteries from swine were harvested and downstream branches (1A and 3A) were isolated, mounted in a pressure myograph, and set to a resting intraluminal pressure of 60 mmHg. Myogenic tone was recorded and vasomotor responses to alpha-1 adrenergic agonism (phenylephrine) were compared in 1A ( n = 6) vs. 3A ( n = 7) arteries. Resting myogenic tone was greater in 3A vs. 1A arteries (13 ± 8% vs. 24 ± 8%, P = 0.023) and alpha-1 adrenergic-mediated vasoconstriction was less in 3A vs. 1A arteries (15 ± 9% vs. 30 ± 9%, P = 0.012). This finding suggests increased myogenic tone does not potentiate alpha-1 adrenergic vasoconstriction. Subsequently, to examine the role of myogenic tone independent of arterial branch order, cerebral vasomotor responses to alpha-1 adrenergic agonism (phenylephrine) were assessed in 1A arteries at high (80 mmHg; n = 4) vs. low (40 mmHg; n = 4) intraluminal pressure. Myogenic tone was greater in high- vs. low-pressure conditions (35 ± 6% vs. 19 ± 14%, P = 0.036) and alpha-1 adrenergic-mediated vasoconstriction was lower in high- vs. low-pressure conditions (5 ± 9% vs. 16 ± 10%, P = 0.003). To isolate the role of myogenic tone from differences in intraluminal pressure, 1A arteries were pre-treated with the L-type calcium channel blocker nifedipine. Differences in myogenic tone between the high (80 mmHg; n = 4) and low (40 mmHg; n = 4) intraluminal pressures were abolished in arteries pre-treated with the L-type calcium channel blockade (14 ± 14% vs. 9 ± 7%, P = 0.400). L-type calcium channel blockade likewise attenuated differences in alpha-1 adrenergic-mediated vasoconstriction at high- vs. low-pressure conditions (3 ± 2% vs. 10 ± 8%, P = 0.105). Altogether, these data indicate reduced myogenic tone is associated with increased alpha-1 adrenergic-mediated vasoconstriction and this effect may be partially modulated by L-type calcium channels. Funding: NSERC Discovery Grant (#05323) This abstract was presented at the American Physiology Summit 2025 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.