Characterization of the contractile 5-hydroxytryptamine receptor in the autoperfused kidney of L-NAME hypertensive rats.

We evaluated the renal vascular effects of serotonin in Nomega-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 microg/kg) increased renal perfusion pressure in a dose-dependent manner, but did not affect systemic blood pressure. The selective 5-HT(2) receptor agonist alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT) caused a local vasoconstrictor effect in the autoperfused rat kidney. The selective 5-HT(2B) receptor agonist BW723C86, the non-selective 5-HT(2C) receptor agonist (1-(3-chlorophenyl) piperazine), m-CPP, the 5-HT(1) receptor agonist 5-carboxamidotryptamine (5-CT) and the selective 5-HT(3) receptor agonist (1-(m-chlorophenyl)-biguanide), m-CPBG, did not modify renal perfusion pressure. The vasoconstrictor effect elicited by alpha-methyl-5-HT was significantly decreased by the 5-HT(2) receptor antagonist ritanserin and the 5-HT(2A) receptor antagonist spiperone, but was not modified by pretreatment with the selective 5-HT(2B/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-HT(2A) 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-HT(2A) receptor.