Alpha adrenergic stimulation is known to produce vasoconstriction. We have earlier shown that, in spiral strips of small arteries Phenylephrine (PE) caused vasorelaxation under high nitric oxide (NO) environment. However, on further experimentation it was realized that the PE-induced vasorelaxant response occurred only with longitudinal strips of small arteries even under normal NO environment while circular strips showed contraction with PE even under high NO environment. Such PE-induced vasorelaxation of longitudinal strips was blocked by Phentolamine, an alpha-adrenergic receptor blocker. On delineation of specific receptor subtype, PE-induced relaxation was found to be mediated through alpha 1D receptor. However, this phenomenon is specific to small artery, as longitudinal smooth muscle of aorta showed only contractile response to adrenergic stimulation. There is no prior report of longitudinal smooth muscle in small artery up to our knowledge. The results of this study and histological examination of vessel sections suggest the presence of longitudinal smooth muscle in small artery and their relaxant response to alpha adrenergic stimulation is a novel phenomenon. Phenyl ephrine relaxes longitudinal strips of small arteries PLOS ONE | https://doi.org/10.1371/journal.pone.0227316 March 3, 2020 2 / 17 PE induces relaxation of longitudinal smooth muscle of small artery both under normal and high NO environmentsPE 100μmol/L reduced the tension of longitudinal smooth muscle from 0.25g to 0.09g in small arteries. (Median, n = 5, P value = 0.043, WSR), Fig 5, (i)). While L-Arginine 100μmol/L did not reduce the basal tension by itself, subsequent addition of PE 100μmol/L reduced the tension from 0.28 to 0.07g (Median, n = 5, P value = 0.043, WSR), Fig 5, (ii). Fig 4. (A) Raw tracing showing changes in vascular tension with PE 100μmol/L in transverse cylinder preparation of small artery. (B) Scatter plots of results from all five experiments demonstrating change in vascular tension with PE from baseline. ( � p = 0.043, WSR), (i) PE 100μmol/L (ii) PE in the presence of L-Arginine (iii) PE in the presence of NO synthase blocker L-NNA.

Alpha adrenergic stimulation is known to produce vasoconstriction. We have earlier shown that, in spiral strips of small arteries Phenylephrine (PE) caused vasorelaxation under high nitric oxide (NO) environment. However on further experimentation it was realized that the PE-induced vasorelaxant response occurred only with longitudinal strips of small arteries even under normal NO environment while circular strips showed contraction with PE even under high NO environment. Such PE-induced vasorelaxation of longitudinal strips was blocked by Phentolamine, an alpha-adrenergic receptor blocker. On delineation of specific receptor subtype, PE-induced relaxation was found to be mediated through alpha 1D receptor. However, this phenomenon is specific to small artery, as longitudinal smooth muscle of aorta showed only contractile response to adrenergic stimulation. There is no prior report of longitudinal smooth muscle in small artery up to our knowledge. The results of this study and histological examination of vessel sections suggest the presence of longitudinal smooth muscle in small artery and their relaxant response to alpha adrenergic stimulation is a novel phenomenon.

Fig 2. (A) Raw tracings showing changes in vascular tension in circular strips of aorta (B) Scatter plots of results from all five experiments demonstrating increase in vascular tension with PE. (C) Quantum of change with PE from baseline ( � p< 0.05). (i) PE 100uM (ii) PE 100uM in high NO environment caused by L-Arginine (iii) PE 100uM in presence of SNP.