Iptakalim: A novel multi-utility potassium channel opener
(Kir6.1s) (Kir6.1s)1★, regulatory sulphonylurea subunits (SUR).[3] IPT shows high selectivity for cardiac KATP (SUR2A/Kir6.2)1, vascular KATP (SUR2B/Kir6.1 or SUR6B/Kir6.2). Because1★ Corresponding author
- 1of this high selectivity, IPT does not exhibit the adverse side effects associated with the older nonspecific K+ channel openers, which limit their use to the treatment of severe or refractory hypertension. IPT produces arteriolar and small artery vasodilatation, with no significant effect on capacitance vessels or large arteries. Vasodilatation is induced by causing cellular hyperpolarization via the opening of K+ channels, which in turn decreases the opening probability of L-type Ca2+ channels. Of particular note, IPT is very effective in lowering the blood pressure of hypertensive humans but not of those with normal blood pressure.[4] Endothelin-1 (ET-1) is a potent vasoconstrictor and comitogen/proliferation factor for vascular smooth muscle. Wang et al. (2005) have shown that IPT reduces ET-1– induced arterial contraction and decreases ET-induced hypertension in rats.[5] They hypothesized that activation of endothelial KATP channels might result in protection against endothelial dysfunction. The mechanism behind endothelial dysfunction, an early risk factor for cardiovascular disease and hypertension, includes reduced nitric oxide (NO) generation and increased ET-1 generation. Wang et al. (2007) first reported that the KATP channel opener, IPT, promotes NO synthase (NOS) activity and NO release; inhibits ET-1 synthesis, and suppresses ET-1 and endothelin converting enzyme (ECE) mRNA expression.[6] Also, Zhao and Wang (2011) have suggested that IPT, via opening KATP channels, enhances the endothelial chemerin/ChemR23 axis and NO production and thus improves endothelial function.[7] Gao et al. (2009) showed that IPT possesses antihypertrophic properties, preventing the progression of left ventricular hypertrophy (LVH) to heart failure induced by pressure overload. Additionally, IPT reduces myocardial and perivascular fibrosis as well as mRNA expression of two important molecular markers of heart failure, viz, atrial natriuretic peptide and B-type natriuretic peptide. The results.
CORRESPONDENCE
(Kir6.1s) (Kir6.1s)
(Kir6.1s),of this high selectivity, IPT does not exhibit the adverse side effects associated with the older nonspecific K+ channel openers, which limit their use to the treatment of severe or refractory hypertension. IPT produces arteriolar and small artery vasodilatation, with no significant effect on capacitance vessels or large arteries. Vasodilatation is induced by causing cellular hyperpolarization via the opening of K+ channels, which in turn decreases the opening probability of L-type Ca2+ channels. Of particular note, IPT is very effective in lowering the blood pressure of hypertensive humans but not of those with normal blood pressure.[4] Endothelin-1 (ET-1) is a potent vasoconstrictor and comitogen/proliferation factor for vascular smooth muscle. Wang et al. (2005) have shown that IPT reduces ET-1– induced arterial contraction and decreases ET-induced hypertension in rats.[5] They hypothesized that activation of endothelial KATP channels might result in protection against endothelial dysfunction. The mechanism behind endothelial dysfunction, an early risk factor for cardiovascular disease and hypertension, includes reduced nitric oxide (NO) generation and increased ET-1 generation. Wang et al. (2007) first reported that the KATP channel opener, IPT, promotes NO synthase (NOS) activity and NO release; inhibits ET-1 synthesis, and suppresses ET-1 and endothelin converting enzyme (ECE) mRNA expression.[6] Also, Zhao and Wang (2011) have suggested that IPT, via opening KATP channels, enhances the endothelial chemerin/ChemR23 axis and NO production and thus improves endothelial function.[7] Gao et al. (2009) showed that IPT possesses antihypertrophic properties, preventing the progression of left ventricular hypertrophy (LVH) to heart failure induced by pressure overload. Additionally, IPT reduces myocardial and perivascular fibrosis as well as mRNA expression of two important molecular markers of heart failure, viz, atrial natriuretic peptide and B-type natriuretic peptide. The results.
Volume 3, Issue 1 · pp. 12–14 · PUBLISHED 2012 · DOI: 10.4103/0976-500X.92495
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ABSTRACT
Hypertension is a multifactorial disorder, and effective blood pressure control is not achieved in most individuals. According to the most recent report of the American Heart Association, for 2010, the estimated direct and indirect financial burden for managing hypertension is estimated to be $76.6 billion. Overall, almost 75% of adults with cardiovascular diseases/ comorbidities have hypertension, which is associated with a shorter overall life expectancy.[1] Alarmingly, rates of prehypertension and hypertension are increasing among children and adolescents due, in part, to the obesity epidemic we currently face. There is also the problem of an aging population and the growing rates of diabetes and obesity in adults, all factors that are associated with high blood pressure.[2] Thus, the need is great for novel drugs that target the various contributing causes of hypertension and the processes leading to end organ damage.
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SELECT FORMAT
(Kir6.1s), K., (SUR2A/Kir6.2), R. S. S. S. I. S. H. S. F. C. K., & Because, V. K. S. O. S. (2012). Iptakalim: A novel multi-utility potassium channel opener. Journal of Pharmacology and Pharmacotherapeutics, 3(1), 12–14. https://doi.org/10.4103/0976-500X.92495