Hypertension is chronic disease with high prevalence, which can successfully be treated with antihypertensive drugs. Previous researches have shown that existing hypertension treatment guidelines are not fully implemented in practice. We have analysed antihypertensive drug utilization in Canton Sarajevo during five-year period (2004-2008). Research findings are discussed in relation to expected drug utilization according to Canton Sarajevo treatment guidelines. Objective of this research is to examine prescription patterns of antihypertensive drugs in primary health care in Canton Sarajevo during five-year period. Based on study findings we did an estimation of adherence to local treatment guidelines, which are similar to those published globally. Drug utilization data were collected from the largest pharmacy (retail) chain, representing more than 80% of pharmacies in Canton Sarajevo. Following drug groups have been analyzed: diuretics, beta-blockers, calcium-channel-blockers, ACE-Inhibitors (plain and combinations), Angiotensin-II-antagonists and alpha-blockers. Drug utilization is expressed in number of defined daily dose (DDDs), defined daily dose per thousand inhabitants per day (DDD/TID), drug utilization 90% (DU90%) and value in euros. ACE-Inhibitors are most prescribed drug class; combination of ACE-Inhibitors and diuretics account 46% of total antihypertensive budget spending. ACEIs are followed by calcium-channel-blockers. Diuretics utilization is decreasing from 2006 and being replaced with beta-blockers. Diuretics, recommended as first line therapy, are ranked as third in total antihypertensive drug utilization. It is necessary to introduce follow-up and enforce adherence to developed treatment guideline. Drug utilization studies can be used as tool for assessment of treatment guidelines adherence in primary health care.

Endothelin 1 (ET-1) is vasoactive peptide that acts via ET-A receptors coupling inducing vascular smooth muscle cell proliferation and contraction. ET-1 is involved in the development and maintenance of hypertension. Aim of this study was to determine the contribution of Ras farnesyl transferase, mitogen activated protein kinase (MAP kinase) and cytochrome P¬450 (CYP450) metabolites to ET-1 induced hypertension. ET-1 (5 pmol/kg per minute) was chronically infused into to the jugular vein by use of mini-osmotic pump for 9 days in male Sprague-Dawley rats. Mean arterial blood pressure (MABP) in ET-1-treated rats was 154±2 mm Hg (hypertensive rats) compared with 98±3 mm Hg in control (normotensive) rats. Infusion of Ras farnesyl transferase inhibitor FPTIII (138 ng/min), MAP kinase inhibitor PD-98059 (694 ng/min) and CYP450 inhibitor 17-ODYA (189 ng/min) significantly attenuated MABP to 115±2.5 mm Hg, 109±3 mm Hg and 118±1.5 mm Hg, respectively. These results suggest that CYP-450 metabolites and Ras/MAP kinase pathway contribute to the development of ET-1 induced hypertension. Further investigation has to be done to confirm whether activation of RAS/MAP kinase pathway by arachidonic acid metabolites plays an important role in the development of ET-1 induced hypertension.