Abstract
AimThe objective was to examine the renal effects of long-term increased angiotensin II and vasopressin plasma levels in early-stage heart failure (HF). We investigated the regulations of the V2 vasopressin receptor, the type 1A angiotensin II receptor, the (pro)renin receptor, and the water channels AQP2, AQP1, AQP3, and AQP4 in the inner medulla of rat kidney.MethodsHF was induced by coronary artery ligation. Sixty-eight rats were allocated to six groups: Sham (N = 11), HF (N = 11), sodium restricted sham (N = 11), sodium restricted HF (N = 11), sodium restricted sham + DDAVP (N = 12), and sodium restricted HF + DDAVP (N = 12). 1-desamino-8-D-arginine vasopressin (0.5 ng h-1 for 7 days) or vehicle was administered. Pre- and post-treatment echocardiographic evaluation was performed. The rats were sacrificed at day 17 after surgery, before cardiac remodeling in rat is known to be completed.ResultsHF rats on standard sodium diet and sodium restriction displayed biochemical markers of HF. These rats developed hyponatremia, hypo-osmolality, and decreased fractional excretion of sodium. Increase of AQP2 and p(Ser256)-AQP2 abundance in all HF groups was blunted compared with control groups even when infused with DDAVP and despite increased vasopressin V2 receptor and Gsα abundance. This was associated with decreased protein abundance of the AT1A receptor in HF groups vs. controls.ConclusionEarly-stage HF is associated with blunted increase in AQP2 and p(Ser256)-AQP2 despite of hyponatremia, hypo-osmolality, and increased inner medullary vasopressin V2 receptor expression. Decreased type 1A angiotensin II receptor abundance likely plays a role in the transduction of these effects.
Highlights
Heart failure (HF) is associated with activation of the renin-angiotensin system (RAS) and sustained increased vasopressin (AVP) release from the pituitary gland [1,2,3,4,5]
Early-stage HF is associated with blunted increase in AQP2 and p(Ser256)-AQP2 despite of hyponatremia, hypo-osmolality, and increased inner medullary vasopressin V2 receptor
We have previously demonstrated that rats with chronic HF 21 days after myocardial infarction (MI) increased the abundance of the renal water channel aquaporin-2 (AQP2) in the inner medullary collecting ducts (IMCDs) [11]
Summary
Heart failure (HF) is associated with activation of the renin-angiotensin system (RAS) and sustained increased vasopressin (AVP) release from the pituitary gland [1,2,3,4,5]. There is increasing evidence of a crosstalk between angiotensin II (ANG II) and AVP with potential enhancing effects on water retention mediated by renal water channels [8,9,10]. We have previously demonstrated that rats with chronic HF 21 days after myocardial infarction (MI) increased the abundance of the renal water channel aquaporin-2 (AQP2) in the inner medullary collecting ducts (IMCDs) [11]. When treated with the type 1A angiotensin II receptor (AT1R) blocker candesartan, HF rats down regulated IMCD AQP2 expression to sham levels [9]. This supports that a crosstalk between the V2 vasopressin receptor (V2R) and AT1R is possible and potentially important in AQP2 regulation. The constitutively expressed AQP1 including the basolateral aquaporins AQP3 and AQP4 remained unchanged both in rats after water loading and in HF rats [11,12,13]
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