Pharmacological Research 52 (2005) 438–444 Investigation of local ACE activity and structural alterations during development of l-NAME-induced hypertension Ali M. Sharifi a,b,∗ , Nasrin Akbarloo a , Radbod Darabi a a Department of Pharmacology and Cellular and Molecular Research Center, School of Medicine, Iran University of Medical Sciences, P. O. Box 14155-6183, Tehran, Iran b Endocrinology and Metabolism Research Center (EMRC), Tehran University of Medical Sciences, Tehran, Iran Accepted 6 July 2005 Abstract Tonic basal release of nitric oxide (NO) by vascular endothelial cells controls blood pressure (BP) in the basal state. In the present study, we showed how serum and local angiotensin converting enzyme (ACE) alters during development of hypertension in chronic nitric oxide synthase blockade, a non-renin-dependent model of hypertension. Four experiments were performed in which animals were given N ω -nitro-l-arginine methyl ester (l-NAME) (50 mg kg -1 ) for 2, 4, 8 and 12 weeks. The control group rats received tap water. The ACE activity in serum, aorta, heart, kidney and lung was analyzed by high performance liquid chromatography (HPLC) and the structural change in aorta was investigated by measurement of cross-sectional area (CSA). Significant elevation of systolic blood pressure developed in chronically NO-blocked rats compared to controls. These results indicated that ACE activity in aortae and heart was gradually increased during development of hypertension and was more pronounced at higher blood pressure. Furthermore, there was a positive correlation between aortic cross-sectional area and elevation of blood pressure. These observations highlight the importance of the local ACE particularly in organs regulating hypertension (aorta and heart) during development of l-NAME-induced hypertension. © 2005 Published by Elsevier Ltd. Keywords: Nitric Oxide; Tissue ACE activity; Hypertension 1. Introduction Despite the fact that essential hypertension is one of the most prevalent diseases and an important risk factor for car- diovascular morbidity and mortality, the underlying patho- physiological abnormalities leading to the development of the elevated arterial pressure in this disorders remain elusive [22]. In normal blood vessels, endothelium-derived nitric oxide (NO) is continuously released both luminally and ablumi- nally, protecting against platelet aggregation and adhesion [12,14] as well as influencing vascular smooth muscle tone [7,20]. NO is enzymatically synthesized from l-arginine, a process that can be antagonized by substituted l-arginine compounds such as N-nitro-l-arginine methyl ester (l- NAME), which compete for the NO synthase [18]. Several ∗ Corresponding author. Tel.: +98 21 805 8696; fax: +98 21 805 8719. E-mail address: sharifal@yahoo.com (A.M. Sharifi). studies have demonstrated that blockade of NO synthesis leads to a marked rises in systemic blood pressure (BP) [21], suggesting that tonic release of NO controls BP in the resting state. Rats chronically treated with l-NAME provide a new model of hypertensive disease, with decreased NO synthase activity as well as chronic decrease in the arterial wall cyclic GMP content [3]. The NO synthesis blocker, l-NAME, is water soluble and orally active and when given in the drink- ing water to animals produces a prolonged increase in blood pressure over many hours [6]. The renin angiotensin aldosterone system (RAAS) plays a major physiologic role in blood pressure control and sodium volume homeostasis [23]. This system has been suggested to be of importance in pathologic conditions such as high blood pressure and renal complications [17]. Angiotensin convert- ing enzyme (ACE) is a zinc metallopeptidase which plays a major role in regulation of vascular tone by converting the inactive peptide, angiotensin I (Ang I) into vasoconstrictor 1043-6618/$ – see front matter © 2005 Published by Elsevier Ltd. doi:10.1016/j.phrs.2005.07.004 etadata, citation and similar papers at core.ac.uk