Papel da grelina e do receptor GHS-R1a no controle da função renal e hemodinâmica em animais normotensos e hipertensos

Abstract

Ghrelin (GRE) is a 28-amino acid peptide that depends on the acylation of serine at position 3 to act as a signaling molecule on growth hormone secretagogues (GHS-Rs). Its function depends on this interaction and these receptors are expressed in several tissues which may imply multisystemic actions. The objective of this research was to evaluate the responses related to renal and hemodynamic function in normotensive and hypertensive rats through administration of ghrelin and GHS-R1a agonists (MK0677) and antagonists (PF04628935). For this purpose, mice were used as experimental models being normotensive (WT) and spontaneously hypertensive (SHR). The following experimental designs were established: 1) Rats were injected subcutaneously (sc) vehicle (VEH) (NaCl 0,9%), ghrelin (GRE) (10μg / kg), GHS-R1a AT antagonist (PF04628935) (0.4mg / kg), ghrelin + PF0462893 or GHS-R1a agonist AGO (MK0677) (10μg / kg) and maintained in metabolic cages for further urinary and plasma analysis. 2- WT and SHR animals received intravenous (i.v.) injections of ghrelin (10 / kg), PF04628935 (0.4 mg / kg) or a combination of ghrelin and PF04628935 for vascular conductance record. 3 - GHS-R1a receptor expression was evaluated by Western blot in the aortic artery, renal artery, cortex and renal medulla. Metabolic parameters (renal function) revealed significant differences in relation to water and feed intake as well as urinary volumes in both the Wistar and SHR treated groups. The same was observed for free water and creatinine clearance in addition to osmolarity and urinary sodium and potassium levels. Intravenous injection of ghrelin reduced mean blood pressure in both strains without evoking significant chronotropic changes. Ghrelin increased Renal Vascular Conductivity (CVR) in SHR rats. The hypotensive and vasomotor effects (CVR) produced by ghrelin in SHR mice were reversed by the specific antagonism of GHS-R1a with PF04628935 (20 minutes after ghrelin injection), for all analyzes was determined (p <0.05). GHS-R1a receptor expression was shown to be decreased in the renal cortex of SHR animals. Thus, the data obtained suggest possible participation of ghrelin and GHR-S1a receptors in renal function and hemodynamic adjustments of normotensive and hypertensive rats.