RESUMEN
NEW FINDINGS: What is the central question of this study? Chronic intermittent hypoxia (CIH) and one-kidney, one-clip experimental models lead to sympathetic overactivity and hypertension. The present study explored the impact of previous exposure to CIH on one-kidney, one-clip renal hypertension; we hypothesized that CIH potentiates its development. What is the main finding and its importance? The development of one-kidney, one-clip renal hypertension was attenuated by previous exposure to CIH, and this protective effect was eliminated by carotid body denervation. These findings indicate that inputs from peripheral chemoreceptors in CIH-preconditioned rats play a role in preventing the increase in sympathetic activity and arterial pressure induced by one-kidney, one-clip renal hypertension. ABSTRACT: Chronic intermittent hypoxia (CIH) and one-kidney, one-clip (1K, 1C) experimental models lead to sympathetic overactivity and hypertension. We hypothesized that previous exposure to CIH potentiates the development of 1K, 1C renal hypertension. Male rats were divided into the following four groups: Control-1K, 1C, maintained under normoxia followed by 1K, 1C surgery (n = 19); Control-Sham, maintained under normoxia, followed by sham surgery (n = 19); CIH-1K, 1C, exposed to CIH (10 days) and 1K, 1C surgery (n = 19); and CIH-Sham, exposed to CIH and sham surgery (n = 18). Animals were catheterized 8 days after 1K, 1C or Sham surgeries and cardiovascular and respiratory parameters recorded on the following day. Baseline mean arterial pressure was higher in Control-1K, 1C than in Control-Sham rats (P < 0.05) and was higher in CIH-1K, 1C than in CIH-Sham rats (P < 0.05). However, the increase in mean arterial pressure in CIH-1K, 1C animals was significantly blunted in comparison to Con-1K, 1C rats (P < 0.05), indicating that previous exposure to CIH attenuates the development of renal hypertension. Systemic administration of hexamethonium, a ganglionic blocker, promoted a larger hypotensive response in Con-1K, 1C compared with CIH-1K, 1C rats (P < 0.05), suggesting that sympathetic activity was attenuated in rats previously exposed to the CIH protocol. In addition, removal of the carotid bodies before 1K, 1C renal hypertension eliminated the protective effect of CIH preconditioning on the development of the 1K, 1C hypertension. We conclude that previous exposure to CIH attenuates the development of renal hypertension via a carotid body-dependent mechanism.
Asunto(s)
Hipertensión Renal/fisiopatología , Hipoxia/fisiopatología , Riñón/fisiopatología , Animales , Presión Arterial/efectos de los fármacos , Presión Arterial/fisiología , Sistema Cardiovascular/efectos de los fármacos , Sistema Cardiovascular/fisiopatología , Cuerpo Carotídeo/efectos de los fármacos , Cuerpo Carotídeo/fisiopatología , Bloqueadores Ganglionares/farmacología , Hexametonio/farmacología , Hipertensión Renal/inducido químicamente , Riñón/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/fisiopatologíaRESUMEN
NEW FINDINGS: What is the central question of this study? What are the effects of hypoxic preconditioning upon the cardiovascular and respiratory responses to subsequent episodes of chronic intermittent hypoxia? What is the main finding and its importance? The cardiovascular and respiratory responses to a chronic intermittent hypoxia protocol were not altered by previous exposure to intermittent or sustained hypoxia. These findings show that preconditioning to hypoxia produced neither facilitation nor protection from the cardiovascular and respiratory dysfunctions in response to subsequent episodes of chronic intermittent hypoxia in juvenile rats. Rats exposed to chronic intermittent hypoxia (CIH) develop hypertension, which is associated with changes in the coupling of sympathetic and respiratory activities. In this study, we hypothesized that previous preconditioning to intermittent or sustained hypoxia would affect cardiovascular and respiratory changes produced by subsequent protocols of CIH. To test this hypothesis, male Wistar rats were preconditioned to either 10 days of CIH or 24 h of sustained hypoxia (SH). After the initial exposure to hypoxia, rats were maintained in normoxic conditions for 15 days before a new protocol of CIH during 10 days. Cardiovascular and respiratory variables obtained from groups of preconditioned rats were compared with a group of rats exposed to CIH for the first time and also to a group of rats maintained in normoxic conditions throughout the period of time of the respective preconditioning protocol. The data show that CIH produced a similar increase in arterial pressure and heart rate in both CIH and SH preconditioning protocols. Respiratory parameters during basal conditions were also not affected by preconditioning to either CIH or SH. We conclude that previous exposure to CIH or SH preconditioning does not facilitate or prevent the cardiovascular changes produced by CIH.