Abstract
The role of the chromosome 1 blood pressure quantitative trait locus (QTL) on the sympathorenal interaction was studied using congenic strains. The two reciprocal congenic strains, WKYpch1.0 and SHRSPwch1.0, were respectively constructed by introgressing the stroke-prone spontaneously hypertensive rat (SHRSP)−derived fragment for the QTL into a Wistar-Kyoto rat (WKY) and vice versa. The role of the sympathetic nervous system in the kidney was evaluated by comparing the renal functions between denervated and sham-operated kidneys under anesthesia. The denervation was performed by stripping the adventitia off and applying 10% phenol to the blood vessels at the left renal hilus. Polyfructosan was continuously injected intravenously to determine the renal plasma flow and the glomerular filtration rate. A reciprocal and significant alteration in the renal norepinephrine (NE) content was observed between WKY and WKYpch1.0 and between SHRSP and SHRSPwch1.0. Concomitantly, the renal vascular resistance differed significantly between the congenic and the background parental strains. By contrast, no significant difference was observed in the fractional excretion of sodium, an index of the tubular function. While the denervation elicited a significant decrease of the renal NE content in all of the four strains studied, the significant effects of the denervation on the renal functions were observed only in SHRSP and WKYpch1.0, both of which harbored the SHRSP-derived QTL fragment. These results indicated that the chromosome 1 blood pressure QTL modulated the renal functions through the sympathetic nerve activity in the kidney.
Similar content being viewed by others
Article PDF
References
Mancia G, Grassi G, Giannattasio C, Seravalle G : Sympathetic activation in the pathogenesis of hypertension and progression of organ damage. Hypertension 1999; 34: 724–728.
Lee RM, Borkowski KR, Leenen FH, Tsoporis J, Coughlin M : Combined effect of neonatal sympathectomy and adrenal demedullation on blood pressure and vascular changes in spontaneously hypertensive rats. Circ Res 1991; 69: 714–721.
Judy WV, Farrell SK : Arterial baroreceptor reflex control of sympathetic nerve activity in the spontaneously hypertensive rat. Hypertension 1979; 1: 605–614.
Gattone VH 2nd, Evan AP, Overhage JM, Severs WB : Developing renal innervation in the spontaneously hypertensive rat: evidence for a role of the sympathetic nervous system in renal damage. J Hypertens 1990; 8: 423–428.
Caplea A, Seachrist D, Daneshvar H, Dunphy G, Ely D : Noradrenergic content and turnover rate in kidney and heart shows gender and strain differences. J Appl Physiol 2002; 92: 567–571.
Winternitz SR, Katholi RE, Oparil S : Role of the renal sympathetic nerves in the development and maintenance of hypertension in the spontaneously hypertensive rat. J Clin Invest 1980; 66: 971–978.
Cui ZH, Ikeda K, Kawakami K, Gonda T, Nabika T, Masuda J : Exaggerated response to restraint stress in rats congenic for the chromosome 1 blood pressure quantitative trait locus. Clin Exp Pharmacol Physiol 2003; 30: 464–469.
Cui ZH, Ikeda K, Kawakami K, Gonda T, Masuda J, Nabika T : Exaggerated response to cold stress in a congenic strain for the quantitative trait locus for blood pressure. J Hypertens 2004; 11: 2103–2109.
Yamazato M, Ohya Y, Nakamoto M, et al: Sympathetic hyperreactivity to air-jet stress in the chromosome 1 blood pressure quantitative trait locus congenic rats. Am J Physiol Regul Integr Comp Physiol 2006; 290: R709–R714.
Nabika T, Kobayashi Y, Yamori Y : Congenic rats for hypertension: how useful are they for the hunting of hypertension genes? Clin Exp Pharmacol Physiol 2000; 27: 251–256.
Yao H, Cui ZH, Masuda J, Nabika T : Congenic removal of a QTL for blood pressure attenuates infarct size produced by middle cerebral artery occlusion in hypertensive rats. Physiol Genomics 2007; 30: 69–73.
Kato N, Nabika T, Liang YQ, et al: Isolation of a chromosome 1 region affecting blood pressure and vascular disease traits in the stroke-prone rat model. Hypertension 2003; 42: 1191–1197.
Mashimo T, Nabika T, Matsumoto C, et al: Aging and salt-loading modulate blood pressure QTLs in rats. Am J Hypertens 1999; 12: 1098–1104.
Serikawa T : Colourful history of Japan's rat resources. Nature 2004; 429: 15 ( Letter).
Ikeda K, Nara Y, Nabika T, et al: Genetic factors regulate the rise in blood pressure in F2 generation crossed between stroke-prone spontaneously hypertensive rats and Wistar-Kyoto rats. Clin Exp Pharmacol Physiol 1991; 18: 593–597.
Patel KP, Kline RL, Mercer PF : Noradrenergic mechanisms in the brain and peripheral organs of normotensive and spontaneously hypertensive rats at various ages. Hypertension 1981; 3: 682–690.
Fuhr J, Kaczmarczyk J, Kruttgen CD : A simple colorimetric method of inulin determination in renal clearance studies on metabolically normal subjects and diabetics. Klin Wochenschr 1955; 33: 729–730.
Wang T, Takabatake T : Effects of vasopeptidase inhibition on renal function and tubuloglomerular feedback in spontaneously hypertensive rats. Hypertens Res 2005; 28: 611–618.
Kai T, Shimada S, Sugimura K, et al: Tissue-localized angiotensin II enhances cardiac and renal disorders in Tsukuba hypertensive mice. J Hypertens 1998; 16: 2045–2049.
Brodie BB, Costa E, Dlabac A, Neff NH, Smookler HH : Application of steady state kinetics to the estimation of synthesis rate and turnover time of tissue catecholamines. J Pharmacol Exp Ther 1966; 154: 493–498.
Fujita T, Sato Y : Role of hypothalamic-renal noradrenergic systems in hypotensive action of potassium. Hypertension 1992; 20: 466–472.
Wang T, Kobayashi Y, Nabika T, Takabatake T : Enhanced sympathetic control of renal function in rats congenic for the hypertension-related region on chromosome 1. Clin Exp Pharmacol Physiol 2005; 32: 1055–1060.
Nakaya H, Sasamura H, Kitamura Y, et al: Effects of angiotensin inhibitors on renal injury and angiotensin receptor expression in early hypertensive nephrosclerosis. Hypertens Res 1999; 22: 303–312.
Nakaya H, Sasamura H, Hayashi M, Saruta T : Temporary treatment of prepubescent rats with angiotensin inhibitors suppresses the development of hypertensive nephrosclerosis. J Am Soc Nephrol 2001; 12: 659–666.
Esler M, Jennings G, Korner P, et al: Assessment of human sympathetic nervous system activity from measurements of norepinephrine turnover. Hypertension 1988; 11: 3–20.
Iigaya K, Kumagai T, Nabika T, et al: Chromosome 1 quantitative trait locus in congenic strains induces different response of rostral ventrolateral medulla neurons to angiotensin II. Proceedings of the 12th International Symposium on SHR. Kyoto, 2006, p 27.
Hirooka Y, Kimura Y, Nozoe M, Sagara Y, Ito K, Sunagawa K : Amlodipine-induced reduction of oxidative stress in the brain is associated with sympatho-inhibitory effects in stroke-prone spontaneously hypertensive rats. Hypertens Res 2006; 29: 49–56.
Kishi T, Hirooka Y, Kimura Y, Ito K, Shimokawa H, Takeshita A : Increased reactive oxygen species in rostral ventrolateral medulla contribute to neural mechanisms of hypertension in stroke-prone spontaneously hypertensive rats. Circulation 2004; 109: 2357–2362.
Ishiguro K, Sasamura H, Sakamaki Y, Itoh H, Saruta T : Developmental activity of the renin-angiotensin system during the “critical period” modulates later L-NAME–induced hypertension and renal injury. Hypertens Res 2007; 30: 63–75.
DiBona GF, Kopp UC : Neural control of renal function. Physiol Rev 1997; 77: 75–197.
Gebremedhin D, Fenoy FJ, Harder DR, Roman RJ : Enhanced vascular tone in the renal vasculature of spontaneously hypertensive rats. Hypertension 1990; 16: 648–654.
Uyehara CF, Gellai M : Impairment of renal function precedes establishment of hypertension in spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol 1993; 265: R943–R950.
Berecek KH, Schwertschlag U, Gross F : Alterations in renal vascular resistance and reactivity in spontaneous hypertension of rats. Am J Physiol Heart Circ Physiol 1980; 238: H287–H293.
Guyton AC, Coleman TG, Cowley AV Jr, Scheel KW, Manning RD Jr, Norman RA Jr : Arterial pressure regulation. Overriding dominance of the kidneys in long-term regulation and in hypertension. Am J Med 1972; 52: 584–594.
Beach RE : Renal nerve-mediated proximal tubule solute reabsorption contributes to hypertension in spontaneously hypertensive rats. Clin Exp Hypertens A 1992; 14: 685–697.
Rudd MA, Grippo RS, Arendshorst WJ : Acute renal denervation produces a diuresis and natriuresis in young SHR but not WKY rats. Am J Physiol Renal Physiol 1986; 251: F655–F661.
Takabatake T, Ushiogi Y, Ohta K, Hattori N : Attenuation of enhanced tubuloglomerular feedback activity in SHR by renal denervation. Am J Physiol Renal Physiol 1990; 258: F980–F985.
Cowley AW Jr, Roman RJ, Krieger JE : Pathways linking renal excretion and arterial pressure with vascular structure and function. Clin Exp Pharmacol Physiol 1991; 18: 21–27.
Hubner N, Yagil C, Yagil Y : Novel integrative approaches to the identification of candidate genes in hypertension. Hypertension 2006; 47: 1–5.
Jaluria P, Konstantopoulos K, Betenbaugh M, Shiloach J : A perspective on microarrays: current applications, pitfalls, and potential uses. Microb Cell Fact 2007; 6: 4.
Lopez B, Ryan RP, Moreno C, et al: Identification of a QTL on chromosome 1 for impaired autoregulation of RBF in fawn-hooded hypertensive rats. Am J Physiol Renal Physiol 2006; 290: F1213–F1221.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wang, T., Nabika, T., Notsu, Y. et al. Sympathetic Regulation of the Renal Functions in Rats Reciprocally Congenic for Chromosome 1 Blood Pressure Quantitative Trait Locus. Hypertens Res 31, 561–568 (2008). https://doi.org/10.1291/hypres.31.561
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1291/hypres.31.561
Keywords
This article is cited by
-
Renal nerves contribute to hypertension in Schlager BPH/2J mice
Hypertension Research (2019)
-
Synergistical action of the β2 adrenoceptor and fatty acid binding protein 2 polymorphisms on the loss of glomerular filtration rate in Chinese patients with type 2 diabetic nephropathy
International Urology and Nephrology (2018)
-
Importance of rostral ventrolateral medulla neurons in determining efferent sympathetic nerve activity and blood pressure
Hypertension Research (2012)