sodium-nitrite and Coronary-Artery-Disease

Several animal studies suggested that the angiotensin II type 2 (AT2) receptor subtype mediates vasodilation, yet the results in human arteries are less well described and more inconsistent. Therefore, we evaluated the role of the AT2 receptor stimulation on the vasotonus of human internal mammary arteries.. Internal mammary arteries were obtained from 50 patients undergoing coronary bypass surgery. The expression of angiotensin II type 1 (AT1) receptor and AT2 receptor mRNA was determined by using real-time polymerase chain reaction. In addition, angiotensin II and CGP42112A concentration-response curves (concentration range: 10(-10) M to 10(-6) M) were constructed in absence or presence of candesartan (10(-5) M) and/or the AT2 receptor-antagonist PD-123319 (10(-6) M) and/or the alpha receptor antagonist phentolamine.. Both AT1 and AT2 receptor protein and mRNA were detected, and higher AT2 receptor mRNA expression levels were associated with increased contractile response to angiotensin II. Angiotensin II caused vasoconstriction up to 41.1 +/- 6.5% of the maximal response to phenylephrine, and PD123319 significantly reduced this response (28.6 +/- 9.6%, P < 0.001). Candesartan completely blocked the angiotensin II-mediated response (1.4 +/- 3.1%, P < 0.001 versus control), and additional blockade of the AT2 receptor with PD123319 did not change this effect (1.8 +/- 5.1%). Phentolamine (10(-5) M) caused attenuation and rightward shift of the angiotensin II concentration response curves. The AT2 receptor agonist CGP42112A did not induce a significant response.. Although AT2 receptor mRNA is present in human internal mammary arteries, AT2 receptor stimulation does not mediate vasodilation in these arteries.

Topics: Acetylcholine; Adrenergic alpha-Antagonists; Adult; Aged; Aged, 80 and over; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Biphenyl Compounds; Coronary Artery Disease; Female; Gene Expression; Humans; Imidazoles; In Vitro Techniques; Male; Mammary Arteries; Middle Aged; Oligopeptides; Phentolamine; Phenylephrine; Pyridines; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Sodium Nitrite; Tetrazoles; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

This investigation was undertaken to determine whether it was possible to restore endothelium-dependent relaxation (EDR) in the cholesterol-fed rabbit model of atherosclerosis following discontinuation of the cholesterol. New Zealand white rabbits, approximately 8 weeks of age, were randomized into (i) control group (9 animals fed a standard rabbit diet) and (ii) experimental group (27 animals: fed the same diet supplemented with 2.5% cholesterol). The experimental animals were restored to the standard diet after 3 weeks. EDR to acetylcholine (-9.0 to -5.0 log mol/L) was examined in the experimental animals at 3, 7, and 15 weeks after commencement of the study (n = 9 at each stage) and the nine control animals examined after 7 weeks. At the end of 7 weeks, EDR to acetylcholine (-6.0 log mol/L) was significantly (p less than 0.05) impaired in the experimental group (34.3 +/- 3.8%) compared with that in the control group (79.8 +/- 3.0%). The loss of EDR was not apparent in the experimental group at 3 weeks (relaxation: 81.7 +/- 4.7%). At the end of 15 weeks, the EDR was significantly restored in the experimental group (relaxation: 63.6 +/- 5.1%). These findings demonstrate that it is possible to reverse the loss of EDR that occurs with cholesterol feeding in the rabbit by limiting the period of exposure to a high cholesterol diet.

Topics: Acetylcholine; Animals; Aorta, Thoracic; Azo Compounds; Cholesterol, Dietary; Coronary Artery Disease; Disease Models, Animal; Endothelium, Vascular; Lipids; Microscopy, Electron, Scanning; Muscle Relaxation; Muscle, Smooth, Vascular; Organ Size; Rabbits; Sodium Nitrite; Staining and Labeling