Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2009, vol. 18, nr 3, May-June, p. 205–214

Publication type: original article

Language: English

The Role of Renal Sympathetic Nerve Activity in Mediating Renal Hemodynamic Alterations in Rat Models of Renal Impairment

Rola aktywności nerkowych włókien współczulnych w pośredniczeniu w zmianach hemolitycznych nerek na modelu mysim uszkodzenia nerek

Ibrahim M. Salman1,, Munavvar A. Sattar1,, Nor A. Abdullah2,, Omar Z. Ameer1,, Mohammed H. Abdulla1,, Fathihah Basri1,, Nur Jannah M. Hussain1,, MD. Abdul Hye Khan3,, Mun F. Yam1,, Kolla R.L. Anand Swarup1,, Hassaan A. Rathore1,, Raisa N. Kazi1,, Raghava N. Sriramaneni1,, Edward J. Johns4,

1 Department of Cardiovascular and Renal Physiology and Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia

2 Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia

3 Tulane Hypertension and Renal Center of Excellence, Tulane University Health Science Center, New Orleans, USA

4 Department of Physiology, Aras Windle, University College Cork, Cork, Ireland

Abstract

Background. It is well known that the pathogenesis of most renal diseases is associated with alterations in renal hemodynamics and also that the regulation of renal hemodynamics is under the direct control of renal sympathetic nerve activity.
Objectives. The role of the renal sympathetic nervous system in the early deterioration of renal hemodynamics in rats with pathophysiological states of renal impairment was investigated.
Material and Methods. Male Sprague Dawley rats were induced with acute renal failure or diabetes mellitus by cisplatin or streptozotocin (STZ), respectively. Cisplatin−induced renal failure was confirmed by impaired renal function and the diabetic state and early renal impairment were confirmed by hyperglycemia, changes in physiological parameters, and renal function. The hemodynamic study was conducted on anesthetized rats 7 days after cisplatin or STZ administration. During the acute study the renal sympathetic nerves were electrically stimulated at increasing frequencies and the responses in renal blood flow (RBF) and renal vascular resistance (RVR) were recorded in the presence and absence of renal denervation.
Results. In the innervated rats with renal impairment, renal nerve stimulation (RNS) caused significant attenuation (all P < 0.05 vs. innervated control) of the renal vasoconstrictor responses. These responses were markedly (all P < 0.05) abolished when renal denervation was performed; however, they appeared significantly (all P < 0.05) higher than the denervated control counterparts.
Conclusion. The findings strongly suggest an early involvement of renal sympathetic nerve action in the pathogenesis of renal impairment accompanying renal failure and diabetes. The data further suggest an early enhancement of renal sensitivity to intrarenal norepinephrine upon the removal of renal sympathetic tone by denervation.

Streszczenie

Wprowadzenie. Patogeneza większości chorób nerek jest związana ze zmianami hemodynamiki w nerkach. Wiadomo również, że regulacja hemodynamiki w nerkach jest kontrolowana bezpośrednio w wyniku aktywności układu współczulnego.
Cel pracy. Zbadanie roli współczulnego układu nerwowego nerek we wczesnym pogorszeniu hemodynamiki nerek u szczurów z patofizjologicznymi cechami uszkodzenia nerek.
Materiał i metody. U szczurów Sprague Dawley wywołano ostrą niewydolność nerek lub cukrzycę podawaniem, odpowiednio, cisplatyny lub streptozocyny (STZ). Niewydolność nerek indukowana podawaniem cisplatyny była potwierdzona zaburzoną czynnością nerek, a cukrzyca i wczesne uszkodzenie nerek stwierdzeniem hiperglikemii, zmianami w parametrach fizjologicznych i czynności nerek. Badanie hemodynamiczne przeprowadzono na szczurach 7 dni po podaniu cisplatyny lub STZ. Podczas badania nerwy współczulne nerek pobudzano elektrycznie rosnącymi częstotliwościami, a zmiany w nerkowym przepływie krwi i oporze naczyń zapisywano w odnerwieniu i bez odnerwienia.
Wyniki. U szczurów z unerwieniem i uszkodzeniem nerek pobudzanie nerwów powodowało istotne osłabienie odpowiedzi w postaci zwężenia naczyń nerek (p < 0,05 vs grupa kontrolna). Odpowiedzi te były znacząco (p < 0,05) zniesione, gdy przeprowadzono odnerwienie nerek; były jednak istotnie większe (p < 0,05) w porównaniu z odpowiednimi badaniami kontrolnymi szczurów z odnerwionymi nerkami.
Wnioski. Uzyskane wyniki przemawiają za wczesnym udziałem układu współczulnego nerek w patogenezie uszkodzenia nerek towarzyszącego niewydolności nerek i cukrzycy. Dane sugerują również wczesne zwiększenie wrażliwości nerek na wewnątrznerkową noradrenalinę po usunięciu napięcia współczulnego przez odnerwienie.

Key words

renal hemodynamics, renal sympathetic nerve, renal impairment, norepinephrine, cisplatin, streptozotocin

Słowa kluczowe

hemodynamika nerek, unerwienie współczulne nerek, uszkodzenie nerek, noradrenalina, cisplatyna, streptozocyna

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