Role of Ang1‐7 in renal haemodynamics and excretion in streptozotocin diabetic rats

• Published in: Clinical and experimental pharmacology & physiology Vol. 49; no. 3; pp. 432 - 441
• Main Authors: Kuczeriszka, Marta, Dobrowolski, Leszek, Walkowska, Agnieszka, Baranowska, Iwona, Sitek, Joanna D., Kompanowska‐Jezierska, Elżbieta
• Format: Journal Article
• Language: English
• Published: Australia Wiley Subscription Services, Inc 01.03.2022
• Subjects: Acetylcholine; Acetylcholine - pharmacology; Ang1‐7; Angiotensin; Angiotensin I - pharmacology; Animals; Blood circulation; Blood Glucose; Blood pressure; Blood Pressure - drug effects; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental; Diuresis; Diuresis - drug effects; Drinking - drug effects; Excretion; Hemodynamics; Hyperglycemia; kidney; Kidney - blood supply; Kidney - drug effects; Nitric Oxide; Norepinephrine; Norepinephrine - pharmacology; Peptide Fragments - pharmacology; Perfusion; Random Allocation; Rats; Rats, Sprague-Dawley; Renal artery; renal cortical and medullary perfusion; Renal function; Rodents; Streptozocin; Supplements; Sympathomimetics - pharmacology; Vasoactive agents; vasoconstriction; Vasodilator Agents - pharmacology; Vasodilators; Water intake; Water intakes; kidney; Ang1-7; nitric oxide; vasoconstriction; renal cortical and medullary perfusion; diabetes
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/1440-1681.13618

The contribution of angiotensin (1–7) (Ang1‐7) to control of extrarenal and renal function may be modified in diabetes. We investigated the effects of Ang1‐7 supplementation on blood pressure, renal circulation and intrarenal reactivity (IVR) to vasoactive agents in normoglycaemic (NG) and streptozotocin diabetic rats (DM). In Sprague Dawley DM and NG rats, 3 weeks after streptozotocin (60 mg/kg i.p.) or solvent injection, Ang1‐7 was administered (400 ng/min) over the next 2 weeks using subcutaneously implanted osmotic minipumps. For a period of 5 weeks, blood pressure (BP), 24 h water intake and diuresis were determined weekly. In anaesthetised rats, BP, renal total and cortical (CBF), outer (OMBF) and inner medullary (IMBF) perfusion and urine excretion were determined. To check IVR, a short‐time infusion of acetylcholine or norepinephrine was randomly given to the renal artery. Unexpectedly, BP did not differ between NG and DM, and this was not modified by Ang‐1–7 supplementation. Baseline IMBF was higher in NG vs. DM, and Ang1‐7 treatment did not change it in NG but decreased it in DM. In the latter, Ang1‐7 increased cortical IVR to vasoconstrictor and vasodilator stimuli. IMBF decrease after high acetylcholine dose seen in untreated NG was reverted to an increase in Ang1‐7 treated rats. Irrespective of the glycaemia level, Ang1‐7 did not modify BP. However, it impaired medullary circulation in DM, whereas in NG it rendered the medullary vasculature more sensitive to vasodilators. Possibly, the medullary hypoperfusion in DM was mediated by Ang1‐7 activation of angiotensin AT‐1 receptors which are upregulated by hyperglycaemia.