Cardiovascular PharmacologyCharacterization of the contractile 5-hydroxytryptamine receptor in the autoperfused kidney of L-NAME hypertensive rats

Add time:09/06/2019    Source:sciencedirect.com

We evaluated the renal vascular effects of serotonin in Nω-Nitro-l-arginine-hypertensive rats (L-NAME, 30 mg/kg/day, administered over 21 days in drinking water), a model of systemic hypertension with glomerular capillary hypertension and renal disease due to chronic blockade of endogenous synthesis of nitric oxide (NO) and compared with those obtained in normotensive rats.Using several agonists and antagonists of 5-hydroxytryptamine (5-HT), we characterized the receptor subtypes involved in the contractile response to 5-HT in the in-situ autoperfused rat kidney.An intra-arterial (i.a.) bolus injection of 5-HT (0.00000125–0.1 µg/kg) increased renal perfusion pressure in a dose-dependent manner, but did not affect systemic blood pressure. The selective 5-HT2 receptor agonist α-methyl-5-hydroxytryptamine (α-methyl-5-HT) caused a local vasoconstrictor effect in the autoperfused rat kidney. The selective 5-HT2B receptor agonist BW723C86, the non-selective 5-HT2C receptor agonist (1-(3-chlorophenyl) piperazine), m-CPP, the 5-HT1 receptor agonist 5-carboxamidotryptamine (5-CT) and the selective 5-HT3 receptor agonist (1-(m-chlorophenyl)-biguanide), m-CPBG, did not modify renal perfusion pressure. The vasoconstrictor effect elicited by α-methyl-5-HT was significantly decreased by the 5-HT2 receptor antagonist ritanserin and the 5-HT2A receptor antagonist spiperone, but was not modified by pretreatment with the selective 5-HT2B/2C receptor antagonist (3,5-dihydro-5-methyl-N-3pyridinylbenzo[1,2.b:4,5-b′]dipyrrole(1H)-carboxamide hydrochloride), SB206553.The results of protein expression analyses allow us to postulate that the 5-HT2A receptor protein 5HT-SRC is expressed in renal tissue and differentially expressed in the renal artery of hypertensive (L-NAME) rats. Our data suggest that the serotonergic vasoconstrictor response induced in the in-situ autoperfused hypertensive rat kidney would be mediated by local activation of the 5-HT2A receptor.

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