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The contractile response of the mesenteric resistance arteries to prostaglandin F 2α ; effects of simultaneous hyperlipemia–diabetes
Author(s) -
Georgescu Adriana,
Popov Doina
Publication year - 2003
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1046/j.1472-8206.2003.00196.x
Subject(s) - medicine , endocrinology , contractility , prostaglandin f2alpha , myograph , phorbol , contraction (grammar) , chemistry , mesenteric arteries , cyclooxygenase , prostaglandin , protein kinase c , artery , kinase , enzyme , biochemistry
The effect of hyperlipemia associated with diabetes on the contractility of resistance arteries to prostaglandin F 2 α (PGF 2 α ) 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 2 α was recorded by the myograph technique. The results showed that compared with controls, the contractile response to 10 −5 m PGF 2 α 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 2 α 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 2 α 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 PGF 2 α 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 2 α ; 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 2 α was installed; this consists in a reduced effect of cyclooxygenase inhibition, and a altered activity of Ca 2+ dependent K + channels.