NO-LOSARTAN A

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 (AT₁) receptor.² Losartan is a mammalian AT₁ 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).