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.

Unaltered Oxytocin and Vasopressin Plasma Levels in Patients with Schizophrenia After 4 Months of Daily Treatment with Intranasal Oxytocin

“…This lack of effect is consistent with a recent study demonstrating that prolonged s.c. administration of OXT (20–100 ng/kg/h, 28 days) exerts no changes on heart rate or blood pressure in rats . The same study also reported that prolonged administration of OXT did not change plasma concentrations of atrial natriuretic peptide and renin, nor plasma osmolality . Consistently, plasma osmolality and sodium concentrations were also found to be unaffected by chronic intranasal OXT treatment in our experimental clinical settings.…”

“…Because no previous studies had reported on blood pressure effects of chronic OXT administration in humans, we showed for the first time that the mean systolic pressure values remained unaltered after 4 months of OXT treatment in a group of normotensive patients with schizophrenia. This lack of effect is consistent with a recent study demonstrating that prolonged s.c. administration of OXT (20-100 ng/kg/h, 28 days) exerts no changes on heart rate or blood pressure in rats (38). The same study also reported that prolonged administration of OXT did not change plasma concentrations of atrial natriuretic peptide and renin, nor plasma osmolality (38).…”

Sex dimorphism in ANGII-mediated crosstalk between ACE2 and ACE in diabetic nephropathy

“…We now studied both sexes in the context of ANGII infusion, diabetes, and ACE2 deficiency, and focused our approach on kidney function and histopathology. It is accepted that ANGII promotes cardiac hypertrophy, hypertension, albuminuria, GFR decrease, and tubular injury [55][56][57][58][59]. Here we report a sex dimorphism on these effects.…”

Oxytocin and cardioprotection in diabetes and obesity

“…We would thus expect that AVP signaling is detrimental in this context, and OT is favorable. However this statement may not be accurate in view of the recent study by Phie et al [ 32 ]. They demonstrated that in the rat model of Ang II-induced hypertension, chronic co-treatment with OT failed to prevent the increase of blood pressure and LV hypertrophy.…”