Differential response of angiotensin peptides in the urine of hypertensiveanimals

Urinary excretion rates of angiotensin I (Ang I), angiotensin II (Ang II), and angiotensin-(1-7) [Ang-(1-7)] were determined in normotensive Sprague D awley (SD), spontaneously hypertensive (SHR), and mRen-2 transgenic hyperte nsive animals before and following blockade of Ang II synthesis or activity for two weeks. This study was performed to determine for the first time wh ether inhibition of Ang II alters the excretion of angiotensin peptides in the urine. Rats were given either tap water or water medicated with lisinop ril, losartan or both agents in combination. Blood pressure was monitored a t regular intervals during the experiment by the tail-cuff method, and once again at the end of the study with a catheter implant into a carotid arter y. Metabolic studies and 24 h urinary excretion variables and angiotensin p eptides were determined before and during the procedures. While all three t reatments normalized the blood pressure of hypertensive animals, therapy wi th either lisinopril or the combination of lisinopril and losartan had a gr eater antihypertensive effect in both SHR and [mRen-2]27 transgenic hyperte nsive rats. In the urine, the concentration of the angiotensins (normalized by 24-h creatinine excretion) was several-fold higher in the untreated hyp ertensive animals than in normotensive SD rats. In SD rats, lisinopril or l isinopril and losartan produced a sustained rise in urinary levels of Ang-( 1-7) without changes in the excretion of Ang I and Ang II. In contrast, Ang I and Ang-(1-7) were significantly elevated in SHR medicated with lisinopr il alone or in combination with losartan. Only losartan, however, augmented urinary levels of Ang II in the SHR. The antihypertensive effects of the t hree separate regimens had no effect on the urinary excretion of angiotensi n peptides in [mRen-2]27 transgenic hypertensive rats. These data show that Ang I and Ang-(1-7) are excreted in large amounts in the urine of SD, SHR and [mRen-2]27 hypertensive rats. The unchanged Ang-(1-7) excretion in tran sgenic hypertensive (Tg(+)) rats after inhibition of the renin-angiotensin system agrees with the previous finding of a reduced plasma clearance of th e peptide in this model of hypertension. The data suggest that this form of hypertension may be associated with increased activity of an endogenous co nverting enzyme inhibitor. (C) 1999 Published by Elsevier Science B.V. All rights reserved.