Effect of gap junction uncoupler heptanol on resistance arteries reactivity in experimental models of diabetes, hyperlipemia and hyperlipemia-diabetes.
The understanding of the involvement of the gap junctions (GJ) in the vascular reactivity is an ongoing effort. In this study we questioned on impact of pathologies such as diabetes, hyperlipemia, and simultaneous hyperlipemia-diabetes on GJ involvement in the contractile/relaxant response of the mesenteric resistance arteries. To this purpose, four groups of Golden Syrian hamsters were used: (i) diabetics (D), injected by streptozotocin, (ii) hyperlipemics (H), fed the standard chow of the species supplemented with 3% cholesterol and 15% butter, (iii) simultaneously hyperlipemic-diabetics (HD), and (iv) controls (C), age-matched normal healthy animals. At 24 weeks after the beginning of the experiment, the vascular reactivity of the resistance arteries was measured by the myograph technique in the presence/absence of 1 mM Heptanol (Hep) and of vasoconstrictors and vasodilators. The results showed that: (i) in pathological conditions 1 mM Hep significantly impaired the constrictor response of the hamster resistance arteries to both 10(-5) M NA (noradrenaline, agonist of alpha(1)-adrenoceptors) and 64.1 mM K+ (potassium ion, the major intracellular cation). The impairment occur in the group range: HD < H < D < C being the highest at the simultaneous insult of hyperlipemia and diabetes; (ii) independently of the pathological condition, 1 mM Hep abolishes both endothelium-dependent and independent relaxation of the hamster resistance arteries. At 1 mM Hep we noticed a reversible effect on endothelium-dependent relaxation that may be partially restored (in normal) in the presence of L-arginine. It is hoped that these results may contribute to understanding of the involvement of GJ in vascular pathology/dysfunction.
Georgescu
Adriana
A
Institute of Cellular Biology and Pathology Nicolae Simionescu, Bucharest, Romania. adriana.georgescu@icbp.ro
Alexandru
Nicoleta
N
Constantinescu
Elena
E
Popov
Doina
D
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002791:Cholesterol, Dietary; D006224:Cricetinae; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D017629:Gap Junctions / Q000187:drug effects* / Q000648:ultrastructure; D019850:Heptanol / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D008647:Mesocricetus; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D013311:Streptozocin; D014655:Vascular Resistance; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
D002791:Cholesterol, Dietary; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D013311:Streptozocin; D011189:Potassium Chloride; D019850:Heptanol; D001120:Arginine; D000109:Acetylcholine; D009638:Norepinephrine