Spontaneously hypertensive rats (SHR) are frequently used as rat models of essential hypertension. The mechanism for the development of hypertension is complicated and it is unknown. The renin-angiotensin system (RAS) plays a key role in the control of blood pressure. Microarrays are a powerful tool for studying genetics. The purpose of this study was to investigate changes of gene expression in the heart tissues of SHR after losartan treatment to provide basic data that is useful in the early diagnosis of hypertension and gene treatment.

Rats were divided into three groups: the control (C) group; the hypertension (H) group (SHR), and the losartan (L) group; treated with losartan (10 mg/kg/day) in SHR. Rats were sacrificed at week 5 and microarray analysis was performed.

102 gene expressions including the genes associated with cell proliferation such as Raf1, Uchl1, Btla, Spock1 were increased. The other 139 gene expressions, including the genes related to the regulation of metabolism such as TFIID, Auf1, Bmp, Hub, Taf51 showed decreases in gene expression. A total of 31 genes were differentially expressed in the L group compared to the H group. Of these, 16 genes including the genes associated with macromolecule metabolism such as MGC105766, Ppp1r1a, Rpl3l showed increased expression. The other 15 genes including the genes associated with primary metabolism such as Mcpt4, Ngn3, Tdo, Ak2 Hyal2 showed decreased expressions.

According to microarray analysis, there was significant gene expression change in SHR compared with normal rats as well as significant gene expression changes after losartan treatment in SHR.

Although angiotensin converting enzyme inhibitors have provided plausible effect for the management of hypertension and congestive heart failure, it does have drawbacks such as dry cough in as much as 15 to 30% of patients and incomplete blocking of angiotensin II production. Losartan(Cozaar®) is the first angiotensin II receptor antagonist that has become clinically available as an antihypertensive agent. Because the agent effectively blocks the final common pathway of renin-angiotensin system, it is recognized as an ideal drug for the treatment of hypertension.

We tested the antihypertensive effect and clinical safety of Losartan(Cozaar®) 50mg/day in 22 patients(male : 12, female : 10, age : 51±11, range : 33-70) with stage I and II hypertension from July 1998 to October 1999. The patients were enrolled in the study after two weeks of washout period if the patient was using other antihypertensive drugs. Blood pressure and side effects were monitored at zero, second, sixth, and twelfth week. Baseline chemistry was done before drug administration and follow-up chemistry was done at twelfth week.

Losartan(Cozaar®) showed good patient compliance and good antihypertensive effect without significant changes of laboratory results or clinical complications. At twelfth week, mean systolic blood pressure dropped l9mmHg, and mean diastolic blood pressure dropped 11mmHg. The heart rate showed no significant change during the study period. Blood pressure was controlled below 140/90mmHg in 12(54.5%) patients with Losartan 50mg/day. Five patients complained of minor side effects(dizziness, facial numbness, epigastric discomfort, etc) but no patients discontinued medication due to side effects.

Losartan(Cozaar®) is a safe and effective antihypertensive agent for the treatment of stage I and II hypertensive patients as a single once-a-day treatment.