RESUMO
The splanchnic (SPL) nerve is a postganglionic sympathetic nerve involved in the tonic regulation of the cardiovascular system. Electrical stimulation of this nerve produces mesenteric vasoconstriction and it has been assumed that vasodilatory responses are dependent on inhibition of the vasoconstrictor tone. Several different central stimuli have been shown to dilate the hindquarter vascular bed and constrict the mesenteric vascular bed. To determine whether vasodilatory and vasoconstrictor effects in different vascular beds are elicited by activation of different sympathetic nerves, we investigated the hemodynamic changes in hindquarter, mesenteric and renal vascular beds evoked by electrical stimulation of the SPL nerve. Stimulation of the intact or sectioned SPL nerve in chloralose-anesthetized, artificially ventilated rats evoked increases in the hindquarter vascular conductance and simultaneously decreased the mesenteric and renal vascular conductance. Intravenous (i.v.) administration of L-NAME prior to stimulation of the proximal end of the sectioned SPL nerve abolished the increase in hindquarter conductance, suggesting the involvement of nitric oxide in this response. In assessing the hemodynamic effects of tonic activity on the SPL nerves, no significant changes were observed after unilateral section of the SPL nerve, but bilateral section of the SPL nerves decreased hindquarter conductance and did not significantly change the mesenteric conductance simultaneously. No consistent response was observed in the renal vascular bed after unilateral and subsequent contralateral section of the SPL nerves. These findings demonstrate that electrical stimulation of the SPL nerve produces mesenteric vasoconstriction and simultaneous hindquarter vasodilatation, which is mediated by nitric oxide. Moreover, the present data suggest that SPL nerves may provide a tonic vasodilatory tone in the hindquarter vascular bed and simultaneously a vasoconstrictor tone in another, undetermined vascular bed.
Assuntos
Hemodinâmica/fisiologia , Nervos Esplâncnicos/fisiologia , Análise de Variância , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Pressão Sanguínea/efeitos da radiação , Denervação , Relação Dose-Resposta à Radiação , Estimulação Elétrica/métodos , Inibidores Enzimáticos/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Frequência Cardíaca/efeitos da radiação , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/efeitos da radiação , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/inervação , Artérias Mesentéricas/fisiologia , NG-Nitroarginina Metil Éster/farmacologia , Ratos , Ratos Wistar , Circulação Renal/efeitos dos fármacos , Circulação Renal/fisiologia , Circulação Renal/efeitos da radiação , Circulação Esplâncnica/efeitos dos fármacos , Circulação Esplâncnica/fisiologia , Circulação Esplâncnica/efeitos da radiação , Nervos Esplâncnicos/efeitos dos fármacos , Nervos Esplâncnicos/efeitos da radiaçãoRESUMO
In order to evaluate the progression of renal disease, Munich-Wistar rats were submitted to 5/6 nephrectomy and given whole-body x- or gamma-irradiation with or without remnant kidney protection or were submitted only to remnant kidney irradiation. All groups received a single 6-Gy dose immediately after surgery. Whole-kidney function, glomerular hemodynamics, 24-hour proteinuria and histopathology were assessed 60 days after surgery and irradiation. The irradiated nephrectomized animals presented whole-kidney function parameters comparable to those of normal rats. In addition, they were less hypertensive and had higher hematocrit. They showed glomerular hyperfiltration and hypertension even greater than their respective nephrectomized controls. However, the interrelations among the glomerular filtration determinants were somewhat different in irradiated animals. Their 24-hour proteinuria was significantly lower and the sclerosis index and tubulointerstitial injury score were markedly smaller. Among irradiated animals, the worst sclerosis index was observed in those with a shielded remnant kidney and the best in those without protection of the remnant kidney. This led us to speculate about a possible influence of resident mesangial cells on the early events following renal mass ablation and on the maintenance of subsequent physiopathologic changes. Therefore, radiation undoubtedly provoked a beneficial change in the course of renal disease when the renal mass ablation model was employed. Many factors could have contributed to this favorable feature including lower levels of systemic arterial pressure, less increment in DeltaP, diminished proteinuria, and maintenance of tubulointerstitial space integrity. Our data also suggest that development of glomerulosclerosis seems to be determined by events occurring immediately after injury.
Assuntos
Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/radioterapia , Glomérulos Renais/fisiopatologia , Glomérulos Renais/efeitos da radiação , Circulação Renal/efeitos da radiação , Animais , Modelos Animais de Doenças , Progressão da Doença , Glomérulos Renais/irrigação sanguínea , Masculino , Nefrectomia , Proteinúria/fisiopatologia , Proteinúria/radioterapia , Ratos , Ratos Wistar , Irradiação Corporal TotalRESUMO
While arterial hypertension and renal dysfunction are well recognized complications of renal irradiation, the mechanisms that trigger the development of these complications are unknown. Recently, it was reported that the endothelium is a major target in radiation injury. Because dysfunction of the endothelial cells may lead or contribute to the development of hypertension and renal dysfunction in radiation nephropathy, we tested the hypothesis that endothelium-dependent vasodilation is impaired in radiated kidneys prior to the onset of hypertension. To test this hypothesis, we used Long-Evans rats that had undergone left nephrectomy (3 weeks earlier) and irradiation (3000 r's) to the right kidney 8 days earlier (mean blood pressures in the irradiated rats were not different than in the controls). We then measured the changes in renal blood flow (RBF) induced by endothelium-dependent (acetylcholine and bradykinin) and -independent (nitroprusside, norepinephrine, and angiotensin II) vasoactive agents. We found that the increases in RBF induced by the endothelium-dependent but not independent vasodilators were markedly impaired in the irradiated kidneys. Blocking nitric oxide synthesis with nitro L-arginine methyl ester in sham rats mimicked the blunted responsiveness of the irradiated rats, whereas indomethacin (an inhibitor of prostaglandin synthesis) had no effect on either sham or irradiated rats. Finally, the RBF responses to the endothelium-independent vasoconstrictors, norepinephrine and angiotensin II, were not altered in the irradiated kidneys. These results suggest that renal irradiation causes endothelial dysfunction (prior to the onset of hypertension) but spares the vascular smooth muscle cells.