Description
Angiotensin II is a hormone that plays an important role in regulating blood pressure.
1 Elevated levels of angiotensin II are implicated in inducing and maintaining hypertension, and also in the development of atherosclerosis. Both of these effects are mediated by the angiotensin II type 1 (AT
1) receptor.
2 Losartan is a mammalian AT
1 receptor antagonist with a K
i value of 5-
20 nM.
3 In humans, losartan effectively controls hypertension while protecting renal function.
4 Nitric oxide (NO) causes vasodilation and also inhibits platelet and neutrophil aggregation in the endothelium.
5,6 NO-
losartan A possesses similar anti-
hypertensive effects to losartan, with the addition of the vasodilating effects of NO release.
7
References
1. Ortiz, M.C., Sanabria, E., Manriquez, M.C., et al. Role of endothelin and isoprostanes in slow pressor responses to angiotensin II Hypertension 37(2),505-511(2001).
2. Schiffrin, E.L. Beyond blood pressure: The endothelium and atherosclerosis progression Am. J. Hypertens. 15(10 Pt 2),115S-122S(2002).
3. Ji, H., Leung, M., Zhang, Y., et al. Differential structural requirements for specific binding of nonpeptide and peptide antagonists to the AT1 angiotensin receptor. Identification of amino acid residues that determine binding of the antihypertensive drug losartan J. Biol. Chem. 269(24),16533-16536(1994).
4. Caruso, D., D'Avino, M., Acampora, C., et al. Effects of losartan and chlorthalidone on blood pressure and renal vascular resistance index in non-diabetic patients with essential hypertension and normal renal functions J. Cardiovasc. Pharmacol. 44(5),520-524(2004).
5. Moncada, S., and Higgs, A. The L-arginine-nitric oxide pathway N. Engl. J. Med. 329,2002-2012(1993).
6. Loscalzo, J., and Welch, G. Nitric oxide and its role in the cardiovascular system Prog. Cardiovasc. Dis. 38,87-103(1995).
7. Breschi, M.C., Calderone, V., Digiacomo, M., et al. NO-sartans: A new class of pharmacodynamic hybrids as cardiovascular drugs J. Med. Chem. 47,5597-5600(2004).
