Participation of adenosine in the renal hemodynamic abnormalities of hypothyroidism.
To investigate the participation of adenosine (ADO) in the abnormalities of renal function associated with hypothyroidism, glomerular hemodynamics were evaluated in normal (Nl) and 2-wk thyroidectomized (Htx) rats. Studies were performed before and during intravenous infusion of the ADO blocker 1,3-dipropyl-8-p-sulfophenyl xanthine (PSPX, 20 mM, 1.2 ml/h), intra-aortic ADO (100 nmol.kg-1.min-1), or vehicle. In addition, single-nephron glomerular filtration rate (SNGFR) was measured during the infusion of different intrarenal ADO doses (1, 10, and 35 nmol.kg-1.min-1); plasma and renal content of ADO were measured by high-performance liquid chromatography in additional groups. Decreased SNGFR, glomerular blood flow (QA), and ultrafiltration coefficient (Kf) were found in Htx rats. PSPX did not modify glomerular hemodynamics in Nl rats; in contrast, in Htx rats, the antagonist increased SNGFR, QA, and Kf, with a fall in afferent (RA) and efferent (RE) resistances. ADO infusion in Nl rats produced renal vasoconstriction characterized by a fall in SNGFR, QA, and Kf, with an increased RA and RE. Paradoxically, in Htx rats, ADO increased SNGFR, QA, and Kf, decreasing RA and RE. However, when ADO was infused through the renal artery, it induced a 20% reduction of SNGFR at 1 nmol.kg-1.min-1 that rose to control values at 10 nmol.kg-1.min-1 and increased to 38.3% to 35.kg-1.min-1. Renal ADO content was markedly low in Htx rats (4.37 +/- 0.79 and 115.46 +/- 14.9 nmol/g wet wt for Htx and Nl rats, respectively). Renal vasodilation induced by PSPX in Htx rats suggests predominant activation of A1 receptors in this condition. The vasodilatory response to exogenous ADO suggests additional activation of A2 receptors.
Franco
M
M
Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City 14080, Mexico.
Bobadilla
N A
NA
Suárez
J
J
Tapia
E
E
Sánchez
L
L
Herrera-Acosta
J
J
D000241:Adenosine / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001011:Aorta; D002851:Chromatography, High Pressure Liquid; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007037:Hypothyroidism / Q000503:physiopathology*; D007262:Infusions, Intravenous; D007269:Injections, Intra-Arterial; D008297:Male; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation; D013965:Thyroidectomy; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology
D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; C053896:1,3-dipropyl-8-(4-sulfophenyl)xanthine; D000241:Adenosine