The role of nitric oxide in flow-induced and myogenic responses in 1A, 2A, and 3A branches of the porcine middle cerebral artery

• Published in: Journal of applied physiology (1985) 2022-11, Vol.133 (5), p.1228-1236
• Main Authors: Morse, Cameron J, Boerman, Erika M, McDonald, Matthew W, Padilla, Jaume, Olver, T Dylan
• Format: Article
• Language: English
• Subjects: Animals; Enzyme Inhibitors - pharmacology; Middle Cerebral Artery; Nitric Oxide; Nitric Oxide Synthase; Swine; Vasoconstriction - physiology
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00209.2022

Myogenic and flow-induced reactivity contribute to cerebral autoregulation, with potentially divergent roles for smaller versus larger arteries. The present study tested the hypotheses that compared with first-order (1A) branches of the middle cerebral artery, second- and third-order branches (2A and 3A, respectively) exhibit greater myogenic reactivity but reduced flow-induced constriction. Furthermore, nitric oxide synthase (NOS) inhibition may amplify myogenic reactivity and abolish instances of flow-induced dilation. Isolated porcine cerebral arteries mounted in a pressure myograph were exposed to incremental increases in intraluminal pressure (40-120 mmHg; = 41) or flow (1-1,170 µL/min; = 31). Intraluminal flows were adjusted to achieve 5, 10, 20, and 40 dyn/cm of wall shear stress at 60 mmHg. Myogenic tone was greater in 3A versus 1A arteries ( < 0.05). There was an inverse relationship between myogenic reactivity and passive arterial diameter ( < 0.01). NOS inhibition increased basal tone to a lesser extent in 3A versus 1A arteries ( < 0.01) but did not influence myogenic reactivity ( = 0.49). Increasing flow decreased luminal diameter ( ≤ 0.01), with increased vasoconstriction at 10-40 dyn/cm of shear stress ( < 0.01). However, relative responses were similar between 1A, 2A, and 3A arteries ( = 0.40) with and without NOS inhibition conditions ( ≥ 0.29). Whereas NOS inhibition increases basal myogenic tone, and myogenic reactivity was less in smaller versus larger arteries (range = ∼100-550 µM), neither NOS inhibition nor luminal diameter influences flow-induced constriction in porcine cerebral arteries. This study demonstrated size-dependent heterogeneity in myogenic reactivity in porcine cerebral arteries. Smaller branches of the middle cerebral artery exhibited increased myogenic reactivity, but attenuated NOS-dependent increases in myogenic tone compared with larger branches. Flow-dependent regulation does not exhibit the same variation; diameter-independent flow-induced vasoconstrictions occur across all branch orders and are not affected by NOS inhibition. Conceptually, flow-induced vasoconstriction contributes to cerebral autoregulation, particularly in larger arteries with low myogenic tone.