Histamine-induced vasodilation in the perfused kidney of STZ-diabetic rats: role of EDNO and EDHF.
In this study, we have examined the contribution of endothelium-derived nitric oxide (EDNO) and endothelium-derived hyperpolarizing factor (EDHF) to histamine-induced endothelium-dependent relaxation in the perfused kidney of rats treated with streptozotocin (STZ) to induce diabetes. Histamine-induced vasodilatation in the perfused kidney preparations of both control and diabetic animals, which was not significantly different. Sodium nitroprusside (SNP)-induced relaxation was also not affected in diabetic and control rats. In order to isolate the EDHF component of histamine-induced vasodilator response, L-NAME (10(-4)M) and indomethacin (10(-6)M) were added to the Krebs' solution throughout the experiment. TBA (0.5 mM) produced a significant reduction in histamine-induced maximal vasodilator response in both preparations from control and diabetic animals, indicating the involvement of K+ channels in mediating this response. Charybdotoxin (0.05 microM) but not glibenclamide (0.1 microM) produced significant reduction in histamine-induced vasodilator responses. To test the contribution of EDNO in mediating histamine-induced vasodilatation, the vascular preparations were perfused with 20 mM K+ -Krebs' solution to inhibit the EDHF component of the response. Under this condition, histamine-induced vasodilator response was not significantly different in both preparations from control and diabetic rats. Pre-treatment with L-NAME (10(-4)M) attenuated histamine-induced vasodilatation. There was a more significant attenuation in histamine-induced vasodilatation in the vascular preparations from diabetic rats. The vasodilator effect of calcium ionophore A23187 was investigated in preparations from control and diabetic rats to examine receptor dysfunction associated with diabetes. A23187 produced dose-dependent vasodilator response in the preparations from both control and diabetic rats. In conclusion, our results indicate that histamine-induced vasodilatation in the perfused kidney of the STZ-induced diabetic rats is mediated by the two vasodilator components, namely EDHF and EDNO. The EDHF component was not significantly affected by diabetes. However, histamine-induced vasodilatation mediated by the EDNO component was more significantly reduced in diabetic rats. Results have also indicated that the EDHF component of histamine-induced vasodilatation was mediated through Ca2+ -activated K+ channels in perfused kidney preparations from both control and diabetic rats.
Yousif
Mariam H M
MH
Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait. mariam@hsc.edu.kw
D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D045462:Endothelium-Dependent Relaxing Factors / Q000502:physiology; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D001685:Biological Factors; D045462:Endothelium-Dependent Relaxing Factors; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D006632:Histamine