Chronic administration of pharmacological doses of angiotensin 1-7 and iodoangiotensin 1-7 has minimal effects on blood pressure, heart rate, and cognitive function of spontaneously hypertensive rats.

Abstract

Cardiovascular diseases are the principal cause of death worldwide, with hypertension being the most common cardiovascular disease risk factor. High blood pressure (BP) is also associated with an increased risk of poor cognitive performance and dementia including Alzheimer's disease. Angiotensin 1–7 (Ang 1‐7), a product of the renin‐angiotensin system (RAS), exhibits central and peripheral actions to reduce BP. Recent data from our lab reveals that the addition of a non‐radioactive iodine molecule to the tyrosine in position 4 of Ang 1‐7 (iodoAng 1‐7) makes it ~1000‐fold more potent than Ang 1‐7 in competing for the 125I‐Ang 1‐7 binding site (Stoyell‐Conti et al., 2020). Moreover, the addition of the non‐radioactive iodine molecule increases (~4‐fold) iodoAng 1‐7’s ability to bind to the AT1 receptor (AT1R), the primary receptor for Ang II. Preliminary data indicates that iodoAng 1‐7 can also compete for the 125I‐Ang IV binding site with a low micromolar IC50. Thus, our aims were to compare the effects of chronic treatment of the Spontaneously Hypertensive Rat (SHR) with iodoAng 1‐7 (non‐radioactive iodine isotope) and Ang 1‐7 on arterial pressure, heart rate, and cognitive function. For this study, male SHRs were divided into three groups and treated with Saline, Ang 1‐7, or iodoAng 1‐7 administrated subcutaneously using a 28‐day osmotic mini pump. Systolic BP was measured non‐invasively by the tail‐cuff technique. Cognitive function was assessed by Y‐Maze test and novel object recognition (NOR) test. We have demonstrated in SHRs that subcutaneous administration of high doses of iodoAng 1‐7 prevented the increase in heart rate with age, while Ang 1‐7 showed a trend toward preventing the increase in heart rate, possibly by improving baroreflex control of the heart. Conversely, neither Ang 1‐7 nor iodoAng 1‐7 administered subcutaneously affected BP nor cognitive function.