Pharmacological studies of BK and L‐type Ca2+ channel function in mesenteric arteries and veins from obese patients

Abstract

Small mesenteric veins (MV) are important in regulation of blood pressure via their capacitance function, however, our previous studies showed that MV displayed heterogeneity in pharmacological responses across species. For example, the large conductance Ca2+ activated K+ (BK) channels and L‐type Ca2+ channels control basal tone and spontaneous oscillations in tone in rat but not murine MV. It is unknown if BK and L‐type Ca2+ channels function in human MV. Therefore, we tested BK and L‐type Ca2+ channel function in isolated and pressurized MA (mesenteric arteries) (60 mmHg) and MV (4 mmHg) from small segments of jejunum harvested from specimens obtained from obese subjects undergoing gastric bypass surgery. The patients reported here were female, 23–45 years old, with BMI values between 34–54, but without hypertension or diabetes. We measured drug‐induced changes in outside diameter and found that: 1) Norepinephrine (NE) dose‐response curves were similar in MA (n=4) and MV (n=4). 2) Nifedipine completely blocked Bay K 8644 (L‐type Ca2+ channel agonist)‐induced MA and MV constriction. 3) Nifedipine also blocked KCl (20–60 mM)‐induced MA, and KCl (20–40 mM)‐induced MV constriction. 4) At physiological intraluminal pressure, MV, but not MA, displayed basal tone and oscillating constrictions which were blocked by nifedipine or removing extracellular Ca2+. 5) Paxilline, a BK channel blocker, caused a 20% constriction in MA. 6) Paxilline did not constrict MV, but completely inhibited spontaneous oscillations in tone. Our results indicate that both BK and L‐type Ca2+ channels regulate human MA and MV tone, but act via blood vessel specific mechanisms. Pharmacological responses of human MV are similar to those of the rat but not the mouse.