ABSTRACT
The rodent renovascular hypertension model has been used to investigate the mechanisms promoting hypertension. The importance of the carotid body for renovascular hypertension has been demonstrated. As the commissural NTS (cNTS) is the first synaptic site in the central nervous system that receives information from carotid body chemoreceptors, we evaluated the contribution of cNTS to renovascular hypertension in the present study. Normotensive male Holtzman rats were implanted with a silver clip around the left renal artery to induce two-kidney, one-clip (2K1C) hypertension. Six weeks later, isoguvacine (a GABAA agonist) or losartan (an AT1 antagonist) was injected into the cNTS, and the effects were compared with carotid body removal. Immunohistochemistry for Iba-1 and GFAP to label microglia and astrocytes, respectively, and RT-PCR for components of the renin-angiotensin system and cytokines in the NTS were also performed 6 weeks after renal surgery. The inhibition of cNTS with isoguvacine or the blockade of AT1 receptors with losartan in the cNTS decreased the blood pressure and heart rate of 2K1C rats even more than carotid body removal did. The mRNA expression of NOX2, TNF-α and IL-6, microglia, and astrocytes also increased in the cNTS of 2K1C rats compared to that of normotensive rats. These results indicate that tonically active neurons within the cNTS are essential for the maintenance of hypertension in 2K1C rats. In addition to signals from the carotid body, the present results suggest that angiotensin II directly activates the cNTS and may also induce microgliosis and astrogliosis within the NTS, which, in turn, cause oxidative stress and neuroinflammation.
Subject(s)
Hypertension, Renovascular/etiology , Solitary Nucleus/metabolism , Angiotensin II Type 1 Receptor Blockers , Animals , Carotid Body/surgery , Hypertension, Renovascular/pathology , Hypertension, Renovascular/surgery , Male , Rats, Sprague-Dawley , Solitary Nucleus/pathologyABSTRACT
RELEVANCE: Rudgea viburnoides, popularly known as "congonha-de-bugre" or "erva de bugre", is used in folk medicine as hypotensive, blood depurative, anti-rheumatic, diuretic and in the treatment of kidney and bladder pain. AIM: Based on the popularly acclaimed nephron-protective effect of R. viburnoides, we investigated, using rats, the protective effect of this plant extract on gentamicin-induced kidney injury. MATERIAL AND METHODS: Urinary volume, water and food intakes were assessed in adult male Wistar rats (naive or gentamicin-induced model of nephrotoxicity) treated with R. viburnoides extract. Also blood and kidney samples were collected for further laboratory and histological analyses. RESULTS: R. viburnoides leaves extract improved renal function. It also improved the renal function impairments caused by gentamicin-induced nephrotoxicity, as revealed by glomerular filtration rate, urine output and proteinuria. CONCLUSION: R. viburnoides exert renoprotective effect, which may support its popular use for renal diseases treatment.