Antihypertensive Drugs Aliskiren, Nebivolol, and Olmesartan ... : Journal of Cardiovascular Pharmacology (original) (raw)

Original Article

Antihypertensive Drugs Aliskiren, Nebivolol, and Olmesartan Reduce Hypertension by Reducing Endothelial Microparticles and Regulating Angiogenesis

Jain, Moon MPharm*,†; Bhosale, Vivek MD‡,†; Tripathi, Dipti MSc*,†; Singh, Himalaya MSc*,†; Pal, Niharika MPharm*; Hanif, Kashif PhD*,†; Jagavelu, Kumaravelu PhD*,†

*Pharmacology division, Council of Scientific and Industrial Research-Central Drug Research Institute, Lucknow, India;

†Academy of Scientific and Innovative Research, New Delhi, India; and

‡Clinical and Experimental Medicine division, Council of Scientific and Industrial Research-Central Drug Research Institute, Lucknow, India.

Reprints: Kumaravelu Jagavelu, PhD, Pharmacology Division, Room PCS-202, CSIR-Central Drug Research Institute, CDRI/B.S.10/1, sector 10, Jankipuram extension, Sitapur Road, Lucknow 226031, India (e-mail: [email protected]).

This work was supported by the grants from CSIR-CDRI Network project, THUNDER (BSC0102), UNDO (BSC0103) and Senior Research Fellowship for Moon Jain from Council of Scientific and Industrial Research, Government of India and Ramalingaswami fellowship to Kumaravelu Jagavelu from the Department of Biotechnology, Government of India, and University grants commission Senior Research Fellowship to Dipti Tripathi and Junior Research Fellowship to Himalaya Singh.

The authors report no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jcvp.org).

J. Moon, B. Vivek, T. Dipti, and S. Himalaya have contributed equally.

Abstract

The accelerated generation of endothelial microparticles (EMPs) and impaired angiogenesis are the markers of vascular pathology during various cardiovascular and inflammatory conditions including hypertension. Because studies comparing the effects of antihypertensive agents on these 2 parameters are limited, this study was designed to compare the effects of 3 antihypertensive agents: aliskiren, nebivolol, and olmesartan, on the EMP generation and angiogenesis. Changes in the hemodynamic parameters and serum EMP count were determined after 3 weeks of the drug treatments [aliskiren (30 mg/kg), nebivolol (10 mg/kg), or olmesartan (5 mg/kg) per orally] in l-NAME–induced rat model of hypertension. The 3 drugs prevented the rise in blood pressure and EMP count to a similar extent. Furthermore, nebivolol was found to possess more potent and concentration-dependent antiangiogenic activity compared with aliskiren, whereas olmesartan was devoid of such an effect. The EMPs generated by virtue of the respective drug treatments were found to be involved in mediating the antiangiogenic effect of nebivolol and aliskiren. In addition, olmesartan treatment also resulted in the increased eNOS expression. The results of this study show that the antihypertensive drugs, viz. aliskiren, nebivolol, and olmesartan, regulate the vascular health by their differential effects on the EMP generation and angiogenesis.