Abstract
The role of the renin-angiotensin system in the initiation and maintenance of hypertension has been studied extensively. The most commonly used tools for evaluation have been blocking agents for renin, converting enzyme or angiotensin. Extensive studies have been reported and important results obtained with Ang II analogs which act as specific competitive antagonists. Substitution at the one and eight positions of angiotensin II have thus far produced the most important analogs. The two most extensively used blockers to study in vivo effect in addition to pharmacological and structure activity relationship were [Sar1, Ala8] ang II and [Sar1, Ile8] 1 ang II. The latter was shown to be more potent, as an antagonist, while both pep-tides showed some transient agonistic effects. A series of compounds has been synthesized in our laboratory substituting positions 1 and 8 in the search for more potent inhibitors with less agonistic properties. The purpose of the present note is to report the in vivo effect of one such angiotensin blocker, namely [N-methyl He1, He8] 1 ang II which is a more potent angiotensin inhibitor in vitro.
Materials and Methods. Sprague-Dawley female rats, weighing approx 200 g, were used for all experiments. On the day of the experiment, rats were anesthetized with sodium amytal (6 mg/100 g) and the iliac artery and both femoral veins were cannulated with polyethylene tubing (PE 50). The iliac cannula was connected to a pressure transducer for continuous recording of blood pressure. Either saline or angiotensin II blockers in saline were infused into one femoral vein while the other vein was used to administer pressor doses of angiotensin II.
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