title: Prolonged Subcutaneous Administration of Oxytocin Accelerates Angiotensin II-Induced Hypertension and Renal Damage in Male Rats.
abstract: Oxytocin and its receptor are synthesised in the heart and blood vessels but effects of chronic activation of this peripheral oxytocinergic system on cardiovascular function are not known. In acute studies, systemic administration of low dose oxytocin exerted a protective, preconditioning effect in experimental models of myocardial ischemia and infarction. In this study, we investigated the effects of chronic administration of low dose oxytocin following angiotensin II-induced hypertension, cardiac hypertrophy and renal damage. Angiotensin II (40 μg/Kg/h) only, oxytocin only (20 or 100 ng/Kg/h), or angiotensin II combined with oxytocin (20 or 100 ng/Kg/h) were infused subcutaneously in adult male Sprague-Dawley rats for 28 days. At day 7, oxytocin or angiotensin-II only did not change hemodynamic parameters, but animals that received a combination of oxytocin and angiotensin-II had significantly elevated systolic, diastolic and mean arterial pressure compared to controls (P < 0.01). Hemodynamic changes were accompanied by significant left ventricular cardiac hypertrophy and renal damage at day 28 in animals treated with angiotensin II (P < 0.05) or both oxytocin and angiotensin II, compared to controls (P < 0.01). Prolonged oxytocin administration did not affect plasma concentrations of renin and atrial natriuretic peptide, but was associated with the activation of calcium-dependent protein phosphatase calcineurin, a canonical signalling mechanism in pressure overload-induced cardiovascular disease. These data demonstrate that oxytocin accelerated angiotensin-II induced hypertension and end-organ renal damage, suggesting caution should be exercised in the chronic use of oxytocin in individuals with hypertension.
authors.affiliation: College of Public Health, Medical & Veterinary Sciences, James Cook University, Townsville, Queensland 4811 Australia.
authors.forename: James
authors.initials: J
authors.lastname: Phie
authors.affiliation: College of Public Health, Medical & Veterinary Sciences, James Cook University, Townsville, Queensland 4811 Australia.
authors.forename: Nagaraja
authors.initials: N
authors.lastname: Haleagrahara
authors.affiliation: College of Public Health, Medical & Veterinary Sciences, James Cook University, Townsville, Queensland 4811 Australia.
authors.forename: Patricia
authors.initials: P
authors.lastname: Newton
authors.affiliation: College of Public Health, Medical & Veterinary Sciences, James Cook University, Townsville, Queensland 4811 Australia.
authors.forename: Constantin
authors.initials: C
authors.lastname: Constantinoiu
authors.affiliation: College of Public Health, Medical & Veterinary Sciences, James Cook University, Townsville, Queensland 4811 Australia; Centre for Biodiscovery & Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Townsville Queensland 4811, Australia.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Sarnyai
authors.affiliation: College of Public Health, Medical & Veterinary Sciences, James Cook University, Townsville, Queensland 4811 Australia.
authors.forename: Lisa
authors.initials: L
authors.lastname: Chilton
authors.affiliation: College of Public Health, Medical & Veterinary Sciences, James Cook University, Townsville, Queensland 4811 Australia; Centre for Biodiscovery & Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Townsville Queensland 4811, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: Kinobe
mesh_terms: D000804:Angiotensin II / Q000009:adverse effects*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D019703:Calcineurin / Q000378:metabolism; D006332:Cardiomegaly / Q000139:chemically induced*; D006973:Hypertension / Q000139:chemically induced*; D007279:Injections, Subcutaneous; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D010121:Oxytocin / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood
chemical_list: D000804:Angiotensin II; D010121:Oxytocin; D009320:Atrial Natriuretic Factor; D019703:Calcineurin; D012083:Renin