Enhanced Serotonin (5‐HT)‐Mediated Carotid Vessel Constriction From The Fawn Hooded Hypertensive (FHH) Rat

Abstract

Impaired myogenic response associated with an increase in BK (large conductance potassium) channel function was suggested in cerebral resistance vessels of FHH rats. Introgression of BN (Brown Norway) 2.4 Mbp region of chromosome 1 into FHH rats restored the function of these vessels by normalizing BK channel function in an FHH.1BN congenic rat. However, conclusions derived from resistance vessels cannot be extrapolated to conduit vessels such as the carotid or aorta since they differ in structure, function, and expression of contractile proteins. Here we tested agonist‐mediated contraction and the regulatory role of PKC in mediating K channel function using isometric measurement of tension in carotid vessels isolated from FHH and FHH.1BN rats. Serotonin (5‐HT)‐mediated tension is enhanced in carotid rings isolated from FHH rats when compared to FHH.1BN rats. 5‐HT‐mediated constriction is enhanced further more by inhibition of Kv channel (4AP; 1mM) but not BK channel (Paxilline or Iberiotoxin; 100nM) in FHH rats. 5‐HT‐mediated constriction is not affected by PKC activation (PMA; 100nM) in FHH rats but significantly enhanced in FHH.1BN rats. While inhibition of PKC (GF 109203X, 3µM) diminished 5‐HT‐mediated contraction in both strains it has significantly less effect in FHH rats compared to FHH.1BN rats. Together, these results suggest that mutation in the genes located in 2.4 Mbp region of FHH rat may enhance PKC function that inhibit K channels contributing to augmented 5‐HT‐mediated carotid vessel constriction. This research has received partial funding support from the American Heart Association, Scientist Development Grant (13SDG14000006).