Azilsartan decreases renal and cardiovascular injury in the spontaneously hypertensive obese rat.
OBJECTIVE
Angiotensin II type 1 receptor blockers (ARBs) are widely used in treating hypertension. In the present study, we tested the hypothesis that a novel ARB, azilsartan medoxomil (AZL-M) will prevent renal and cardiovascular injury in the spontaneously hypertensive obese rat (SHROB), a model of cardiometabolic syndrome.


METHODS
Male SHROB were treated with vehicle or AZL-M orally for 56 days. Vehicle treated normotensive Wistar-Kyoto (WKY) rats served as controls. The effects of AZL-M on kidney injury, vascular endothelial and heart functions, lipid profile, and glucose tolerance were assessed.


RESULTS
AZL-M demonstrated anti-hypertensive effects along with markedly improved vascular endothelial function in SHROB. In these rats, AZL-M demonstrates strong kidney protective effects with lower albuminuria and nephrinuria along with reduced tubular cast formation and glomerular injury. AZL-M treatment also improved left ventricular heart function, attenuated development of left ventricular hypertrophy, and reduced cardiac fibrosis in SHROB.


CONCLUSIONS
Overall, these findings demonstrate kidney and heart protective effects of AZL-M in SHROB, and these effects were associated with its ability to lower blood pressure and improve endothelial function.
Department of Pharmacology & Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA, abhkhan@mcw.edu.
Md Abdul
MA
Hye Khan
Jan
J
Neckář
Breana
B
Cummens
Geneva M
GM
Wahl
John D
JD
Imig
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000473:pathology; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D010069:Oxadiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011921:Rats, Inbred WKY; D014280:Triglycerides / Q000097:blood; D014664:Vasodilation / Q000187:drug effects
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001786:Blood Glucose; D007328:Insulin; D010069:Oxadiazoles; D020011:Protective Agents; D014280:Triglycerides; D002784:Cholesterol; C557413:azilsartan medoxomil