Selective enhanced constriction and attenuated dilation in leptin deficient mice.

Abstract

We tested responses to endothelin‐1 (ET), interleukin‐6 (IL6) and IL8 in leptin deficient diabetic mice (db/db or ob/ob), in comparison to C57 genetic background mice in the absence or presence of inhibitors. The cremaster muscle of anesthetized (50 mg/kg Nembutal) mice (n=63) was prepared for intravital microscopy. Arteriole(A)/venule(V) pairs were chosen for study; baseline diameters A 26±8 ?m, V 50±13 ?m were not different between strains. Micropipette applied adenosine (10‐4M) was attenuated in A and V from db/db or nitroarginine (LNNA) pre‐treated C57 vs. control C57. Phenylephrine (10‐4M) constriction was unchanged in A, but attenuated in V from db/db, ob/ob or LNNA vs. C57. ET1 dose dependent constriction (C57 logM EC50 ‐10±5 A; ‐5±4 V) was significantly attenuated in either db/db or ob/ob mice, yet enhanced with LNNA pretreatment in C57. Responses to IL6 or IL8 were biphasic and dose dependent in A from C57, while V showed only constriction. Responses to IL6 were blocked by PD142893. IL6 caused only constriction in A and V of ob/ob or db/db. IL8 caused biphasic responses in some diabetics. Leptin deficient diabetes thus shows attenuated constriction to ET1, selective absence of dilation to IL6 and inconsistent absence of dilation to IL8. NIH DK68401