The contractile response of the mesenteric resistance arteries to prostaglandin F2α;: effects of simultaneous hyperlipemia-diabetes

The effect of hyperlipemia associated with diabetes on the contractility of resistance arteries to prostaglandin F-2alpha (PGF(2alpha)) was investigated employing 4 weeks simultaneously hyperlipemic-diabetic (HD), hyperlipemic (H), diabetic (D) and normal hamsters (controls, C). The isometric force produced by explanted arteries in the presence of 10(-8) to 10(-5) m PGF(2alpha) was recorded by the myograph technique. The results showed that compared with controls, the contractile response to 10(-5) m PGF(2alpha) was approx. 2 fold increased in HD group, and approx. 1.75 and 1.62-fold enhanced in H and D groups, respectively. Activation of protein kinase C with 10(-6) M phorbol 12-myristate 13-acetate increased the contractility to PGF(2alpha) in all groups and particularly in HD hamsters (approx. 10.16-fold). Inhibition of cyclooxygenase by indomethacin increased approx. 1.81-fold the arterial contractility to PGF(2alpha) in C group, whereas in H. D and HD hamsters had no effect. Blockage of Ca2+-activated K+-channels with 10(-3) m tetraethylammonium augmented the contraction to PGF(2alpha) approx. 6.43-fold in C group, and at significantly lower levels in H, D and HD groups, i.e. approx. 3.84, 3.72 and 3.33-fold, respectively. The results validate two conclusions: (i) simultaneous insult of hyperlipemia-hyperglycemia is associated with the highest contractility of the resistance arteries to PGF(2alpha); the highest circulating glucose and cholesterol levels, and the enhancement in the protein kinase C pathway underlay the augmented contractility; (ii) no matter the pathology induced (hyperlipemia, diabetes or both simultaneously) a common dysfunctional response to PGF(2alpha) was installed; this consists in a reduced effect of cyclooxygenase inhibition, and a altered activity of Ca2+ dependent K+ channels.