The effects of diabetes, hypothemia and nitric oxide sinthase blockade on vascular escape and tachyphylaxis in the rabbit isolated kidney
The endothelium plays a crucial role in the vascular tone, releasing relaxing and contracting factors ? among the first ones the gas nitric oxide, produced from the amino acid L-arginine and a group of enzimes called nitric oxide synthases (NOS). This study evaluated the effects of L-arginine as well as NOS inibitors on vascular escape and tachyphylaxis of rabbit kidneys. Furthermore the effects of diabetes and hypothermia were studied also.Normal and alloxan treated diabetic rabbit kidneys were perfused with Krebs-Henseleit solution in a non-recirculating system and norepinephrine (NO) 1 microM was infused for three subsequent periods of 20 min each, with an inteval of 10 min for drug wash-out. In the control group L-arginine and D-arginine were added to the solution (both 1 microM) as well as the NOS inibitors L-NMA (10 microM) and LNOARG (10 microM). This group was also submitted to hypothermia (25o C). The kidneys from diabetic animals were separated in non treated and treated with GSH (1 microM) and rutin (1 microM). The treatment with the NOS inibitor LNOARG increased the basal (steady state) pressure (plt;0.001). The L-arginine treatment decreased both basal (plt;0.05) and maximal (plt;0.01) pressures (after NOR infusion). The nitro-methyL-L-arginine treatment increased the maximal pressures (plt;0.05). Diabetes increased both basal (plt;0.001) and maximal (plt;0.001) pressures.In the control kidneys the infusion of NOR promoted an intense vasoconstriction, which was less intense during the second and the third periods of infusion- what is called tachyphylaxis. The kidneys under hypothermia showed tachyphylaxis only in the second period. But the group treated with L-arginine didn?t show tachyphylaxis ? instead the values became higher and higher at each period of infusion of NOR. However we should be cautious about these results since they didn?t reach a plt;0.05 value.The diabetic group showed a substantially decreased escape when compared to control (plt;0.05), but this effect was partially reversed by the treatment with GSH and rutin. In the kidneys from euglycemic rabbits those treated with L-arginine ? but not D-arginine ? showed an increased escape when compared to control. But this result wasn?t significant. Hypothermia showed a decreased escape too that wasn?t significant, either.
Advisor:Geanne Matos de Andrade Cunha; Helena Serra Azul Monteiro; Manassés Claudino Fonteles
School:Universidade Federal do Ceará
Source Type:Master's Thesis
Keywords:Diabetes Mellitus Escape Vascular Nitric Oxide Hypothermia
Date of Publication:11/18/2003