Role of BK Ca channels and PKC in mesenteric artery contractility of diabetic rats

The aim of this study was to analyze the effect of diabetes mellitus (DM), acting through protein kinase C (PKC), on vascular tone associated to BK Ca channel activity in rat mesenteric artery. Methods DM was induced in male Wistar rats by intravenous injection of streptozotocin (STZ, 60mg/kg) and mesenteric artery rings were isolated for isometric force studies. The effects of PKC inhibitor Bisindolymaleimide I (Bis 1) and BK Ca channel activator NS 1619 on phenylephrine induced contractions were evaluated and expressed as % force. Results NS1619 decreased maximal force in control but not in STZ rats (97.4 ± 16 % vehicle v.s. 81.6 ± 25% NS1619, p=0.011, n=7 for ctrl; 84 ± 13% v.s. 71.8 ± 36%, p=0.54, n = 6 for STZ). Bis1 decreased phenylephrine contraction in both control and STZ rats (61.8 ± 33%, p= 0.003, n =8 ctrl; 34 ± 12%, p=0.0001, n=6 for STZ); although inhibition was more prominent in STZ than in ctrl rats (p= 0.005). Relaxation due to nifedipine was higher for STZ (42±15% for ctrl v.s. 19.5 ±17 for STZ, p=0.031, n=6). Conclusions DM leads to elevated PKC and VOCC activity, probably through BK Ca channel inhibition which is not reversible by NS1619. Supported by: C12‐FAI‐03–60.60, UASLP