nitroarginine and Carotid-Artery-Diseases

Cardiovascular disease is the major cause of morbidity and mortality in diabetic patients, which in turn is also associated with low levels of serum testosterone. The working hypothesis was that diabetes might modify the mechanisms involved in the vascular actions of testosterone in isolated rabbit carotid arteries. Testosterone (10(-8)-3x10(-4)M) induced a concentration-dependent relaxation of precontracted carotid arteries, which was higher in diabetic than in control rabbits. In control rabbits neither endothelium removal nor the nitric oxide synthase (NOS) inhibitor N(G)-nitro-l-arginine (l-NOArg, 10(-5)M) modified the relaxant action of testosterone, and the cyclooxygenase (COX) inhibitor indomethacin (10(-5)M) enhanced this relaxation. In contrast, in diabetic rabbits endothelium removal, l-NOArg (10(-5)M) or indomethacin (10(-5)M) inhibited the testosterone induced relaxation. In arteries from diabetic rabbits, eNOS, iNOS and COX-2 expression and testosterone induced release of prostacyclin resulted enhanced in comparison with arteries from control rabbits. Testosterone (10(-4)M) strongly inhibited CaCl(2) (10(-5)-3x10(-2)M) concentration-related contractions of the carotid artery both in control and diabetic rabbits. These results suggest that testosterone relaxes the rabbit carotid artery by blocking the extracellular calcium entry. Diabetes enhances the vasodilator response of the rabbit carotid artery to testosterone by a mechanism that at least includes an increased modulatory activity of the endothelial nitric oxide and an augmented release of COX-2 vasodilator, prostacyclin rather than the absence of COX-1 vasoconstrictor, thromboxane A(2). The hypotestosteronemia observed in diabetic rabbits could be a consequence of the increased expression of iNOS and could contribute to the hyperreactivity of the rabbit carotid artery to testosterone.

Topics: Animals; Apamin; Blood Glucose; Blotting, Western; Calcium; Carotid Arteries; Carotid Artery Diseases; Charybdotoxin; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Dose-Response Relationship, Drug; Endothelium, Vascular; Epoprostenol; Immunoenzyme Techniques; Indomethacin; Male; Nitric Oxide; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Nitroarginine; Potassium; Potassium Channel Blockers; Rabbits; Testosterone; Thromboxane A2; Vasodilation

The influence of carotid artery occlusion (10, 30 and 60 min) on regulatory mechanisms implicated in the vasorelaxant responses of isolated glandular branch of rabbit facial artery to acetylcholine (ACh) and vasoactive intestinal polypeptide (VIP) was examined.. In organ bath studies with arterial rings precontracted with phenylephrine (1 microM), before and after carotid artery occlusion, changes in isometric tension were recorded.. Endothelium-dependent vasorelaxation by ACh and endothelium-independent vasorelaxation by VIP were significantly reduced, started from 30 and 10 min of carotid occlusion, respectively. Inhibitory effect of indomethacin on ACh vasorelaxation was enhanced whilst effect of N(G)-nitro-L-arginine reduced, started from 30 min of carotid occlusion. Sodium nitroprusside-induced vasorelaxation was not changed after carotid occlusion. Inhibition of VIP vasorelaxation by L-N(omega)-nitroarginine-2,4-L-diaminobutyric-amide, was reduced, started from 30 min of carotid occlusion. Forskolin enhanced VIP-induced vasorelaxation in control rings but this effect was reduced started from 30 min of occlusion. In the presence of VIP, vasorelaxant effect of ACh was increased; the increase was reduced, started from 10 min of carotid occlusion.. The present investigation provides evidence for the decreased responsiveness to both, ACh-endothelium-dependent and VIP-endothelium-independent vasorelaxation in rabbit facial artery after carotid occlusion. In addition, the data suggest that ischaemia alters contribution of endothelial nitric oxide (eNO) and prostaglandin to ACh, and vascular smooth muscle's cAMP and neuronal NO to VIP vasorelaxant effects.

Topics: Acetylcholine; Animals; Arteries; Bradykinin; Carotid Artery Diseases; Carotid Artery, Common; Colforsin; Cyclic AMP; Endothelium, Vascular; Epoprostenol; Female; Indomethacin; Ischemia; Male; Muscle, Smooth, Vascular; Nitric Oxide; Nitroarginine; Nitroprusside; Phenylephrine; Rabbits; Sialadenitis; Signal Transduction; Submandibular Gland; Vasoactive Intestinal Peptide; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents