The contractile response of the mesenteric resistance arteries to prostaglandin F2alpha; effects of simultaneous hyperlipemia-diabetes.
The effect of hyperlipemia associated with diabetes on the contractility of resistance arteries to prostaglandin F2alpha (PGF2alpha) 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 PGF2alpha was recorded by the myograph technique. The results showed that compared with controls, the contractile response to 10(-5) M PGF2alpha 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 PGF2alpha 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 PGF2alpha in C group, whereas in H, D and HD hamsters had no effect. Blockage of Ca(2+)-activated K(+)-channels with 10(-3) M tetraethylammonium augmented the contraction to PGF2alpha 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 PGF2alpha; 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 PGF2alpha was installed; this consists in a reduced effect of cyclooxygenase inhibition, and a altered activity of Ca(2+) dependent K(+) channels.
Georgescu
Adriana
A
Institute of Cellular Biology and Pathology Nicolae Simionescu, 8, B.P. Hasdeu Street, PO Box 35-14, Ro-79691, Bucharest, Romania.
Popov
Doina
D
D000375:Aging; D000818:Animals; D001786:Blood Glucose; D006224:Cricetinae; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D015237:Dinoprost / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006949:Hyperlipidemias / Q000150:complications / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology*; D008647:Mesocricetus; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology; D011493:Protein Kinase C / Q000009:adverse effects / Q000378:metabolism; D019789:Tetraethylammonium / Q000494:pharmacology; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects
D001786:Blood Glucose; D024681:Potassium Channels, Calcium-Activated; D019789:Tetraethylammonium; D015237:Dinoprost; D011493:Protein Kinase C; D007213:Indomethacin