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Salma Toma Hanna
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ABSTRACT: Smoking is a leading cause of cardiovascular disease, hypertension, myocardial infarction, and stroke. Nicotine is one of the components of cigarette smoke. Nicotine effects on the cardiovascular system reflect the activity of the nicotine receptors centrally and on peripheral autonomic ganglia. It has been found that cigarette smoke extract-induced contraction of porcine coronary arteries is related to superoxide anion-mediated degradation of nitric oxide. Treatment of rabbit aortas with an oxygen free radicals scavenger attenuated cigarette smoke impairment of arterial relaxation. Treatment of smokers with vitamin C, an antioxidant, improved impaired endothelium-dependent reactivity of large peripheral arteries. Thus it appears that chronic smoking and acute exposure to cigarette smoke extract may alter endothelium-dependent reactivity via the production of oxygen derived free radicals. This review discusses the effects of nicotine on resistance arterioles, compliance arteries, smooth muscle cells, and ion channels in the cardiovascular system. We discuss studies performed on humans, nicotine-exposed animals, and cell cultures yielding varying and inconsistent results that may be due to differences in experimental design, species, and the dose of exposure. Nicotine exposure appears to induce a combination of free radical production, vascular wall adhesion, and a reduction of fibrinolytic activity in the plasma.
Journal of Cardiovascular Pharmacology 04/2006; 47(3):348-58. · 2.29 Impact Factor
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ABSTRACT: Kir6.1 subunit is one of the pore-forming components of K(ATP) channel complex. The endogenous modulation of Kir6.1 subunit function has been largely unknown. Whether acetylcholine modulated the function of Kir6.1 subunit stably expressed in human embryonic kidney (HEK-293) cells was examined in the present study using the whole-cell patch-clamp technique. Acetylcholine from 1-100 microM concentration-dependently stimulated the heteologously expressed and PNU-37883A sensitive Kir6.1 channels (p<0.05). Co-expression of sulphonylurea receptor 1 subunit with Kir6.1 significantly inhibited the stimulatory effect of acetylcholine on K(ATP) currents. Pretreatment of the transfected HEK-293 cells with atropine, alpha-bungarotoxin, mecamylamine, prazocine, propranolol, or dihydro-beta-erythroidine hydrobromide did not alter the stimulatory effect of acetylcholine on Kir6.1 currents. When intracellular ATP was increased from 0.3 mM to 5 mM, acetylcholine at 10 microM still exhibited its stimulatory effect (-16.4+/-2.3 to -25.5+/-3.8 pA/pF, n=8, p<0.05). In conclusion, we have demonstrated an excitatory effect of acetylcholine on Kir6.1 channels, which is mediated neither by an acetylcholine receptor-dependent mechanism, nor by alteration in ATP metabolism.
European Journal of Pharmacology 06/2005; 515(1-3):34-42. · 2.52 Impact Factor
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ABSTRACT: KATP channels are a complex of regulatory sulfonylurea receptor subunits and the pore-forming inward rectifiers such as Kir6.1. Using the whole-cell patch-clamp technique, we investigated the interaction of nicotine with the Kir6.1 subunit as well as the underlying mechanism. Stable expression of Kir6.1 in HEK-293 cells yielded a detectable inward rectifier KATP current. This inward current was significantly inhibited by PNU-37883A and by a specific anti-Kir6.1 antibody. Nicotine at 30 and 100 microM increased Kir6.1 currents by 42 +/- 11.8% and 26.2 +/- 14.6%, respectively (n = 4-6, P < 0.05). In contrast, nicotine at 1-3 mM inhibited Kir6.1 currents (P < 0.05). Nicotine at 100 microM increased the production of superoxide anion (O2) by 20.3 +/- 5.7%, whereas at 1 mM it significantly decreased the production of O2 by 37.7 +/- 4.3%. Coapplication of hypoxanthine (HX) and xanthine oxidase (XO) to the transfected HEK-293 cells resulted in a significant and reproducible increase in Kir6.1 currents (P < 0.05). The stimulatory effect of HX/XO on Kir6.1 current was abolished by tempol, a scavenger of O2. Tempol also abolished the stimulatory effect of 30 muM nicotine on Kir6.1 currents. In conclusion, nicotine stimulates Kir6.1 channel at least in part through the production of O2.
Journal of Cardiovascular Pharmacology 05/2005; 45(5):447-55. · 2.29 Impact Factor
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ABSTRACT: K(ATP) channels are composed of pore-forming subunits Kir6.x and auxiliary subunits SURx. These channels play important roles in modulating the contractility of vascular smooth muscle cells (SMCs) by altering membrane potentials. The molecular basis of K(ATP) channels in vascular SMCs is unclear and the expression of different K(ATP) channel subunits at protein level in various tissues still undetermined. In this study, using an anti-Kir6.1 antibody, we detected the expression of Kir6.1 proteins in rat vascular tissues including mesenteric artery, pulmonary artery, aorta, and tail artery. Kir6.1 proteins were also identified in heart and other non-vascular tissues including spleen and brain, but they were undetectable in liver and kidney. Immunocytochemical study revealed the expression of Kir6.1 proteins in cultured rat thoracic aortic SMCs. Using the whole-cell patch-clamp technique, it was found that the intracellularly applied anti-Kir6.1 antibody significantly inhibited K(ATP) channel currents in HEK-293 cells that were stably transfected with Kir6.1 cDNA. A better understanding of differential expression of Kir6.1 proteins in various vascular and non-vascular tissues may help discern different molecular basis and functions of K(ATP) channel complexes in these tissues.
Biochemical Pharmacology 02/2004; 67(1):147-56. · 4.70 Impact Factor
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ABSTRACT: Protein dephosphorylation mediated by phosphatases represents an important mechanism for modulating the functions of the targeted proteins. Calyculin A has been extensively used as a specific inhibitor of protein phosphatases. However, the effect of calyculin A on K channel currents in vascular smooth muscle cells (SMCs) and the underlying mechanisms had been unknown. It was found in the current study that calyculin A inhibited the whole-cell outward K channel currents in rat tail artery SMCs in a concentration-dependent (median inhibitory concentration, 12.6 n ) and reversible fashion. The extracellular applied calyculin A induced a biphasic change in K current amplitude with an initial transient increase followed by a long-lasting inhibition (n = 6). The intracellularly applied calyculin A (100 nM ) caused a lesser inhibition (33 +/- 1%) of K channel currents than that caused by the extracellularly applied calyculin A (55.3 +/- 8% inhibition) and did not result in an initial increase in K channel currents. The inhibitory effect of the intracellularly applied calyculin A on K channel currents was reversed to a stimulatory effect after ATP was omitted from the intracellular solution. The K currents inhibited by calyculin A were conducted by the iberiotoxin-sensitive K channels in SMCs. Moreover, okadaic acid (0.03-3 microM ) did not cause any significant change in K(Ca) channel currents. In conclusion, calyculin A inhibited K(Ca) channel currents in vascular SMCs. This effect of calyculin A, however, was not mediated by the inhibition of protein phosphatases.
Journal of Cardiovascular Pharmacology 12/2002; 40(5):660-8. · 2.29 Impact Factor
