Advances in Clinical and Experimental Medicine
2011, vol. 20, nr 1, January-February, p. 47–55
Publication type: original article
Language: English
Influence of High Dietary Sodium Intake on Functional Contribution of Renal α1a-Adrenoceptor of SHR
Wpływ dużej podaży sodu w diecie na czynnościowy wkład α1a-adrenoceptora u szczurów z samoistnym nadciśnieniem tętniczym
1 School of Pharmaceutical Sciences, University Sains Malaysia, 11800, Penang, Malaysia
2 Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
3 Department of Pharmacology and Toxicology, Medical College of Wisconsin, Wisconsin, USA
4 Department of Physiology, Western Gateway Building, University College Cork, College Road, Cork, Ireland
Abstract
Background. Elevated dietary sodium intake exacerbates the elevation of blood pressure in spontaneously hypertensive rats (SHR) which is associated with increased renal vascular resistance and fluid reabsorption. The renal sympathetic nerves exert their action via α1-adrenoceptors (α1-AR) with α1A as the major subtype in regulating renal hemodynamics and excretory function.
Objectives. This study investigated whether the contribution of α1A-AR in regulating renal vasoconstriction and excretory function was enhanced in SHR receiving high sodium intake.
Material and Methods. SHR received either water (SHRNNa) or normal saline (SHRHNa) for six weeks. Metabolic cage studies followed by acute experiments were carried out on these SHR to examine renal vasoconstrictor and excretory responses to catecholamine viz. noradrenaline (NA), phenylephrine (PE) and methoxamine (ME) in the presence and absence of a α1A-AR blocker, 5-methylurapidil (5-MeU).
Results. Daily water intake and urine output were increased in SHRHNa (P < 0.05 vs. SHRNNa). Renal cortical vascular responses to NA, PE and ME were enhanced in SHRHNa (P < 0.05 vs. SHRNNa) and the greatest effect was seen with ME. Intra-renal infusion of PE caused antidiuresis and antinatriuresis. Irrespective of the sodium intake, 5-MeU markedly blunted adrenergically induced renal cortical vasoconstrictions in SHR, while the antinatriuretic and antidiuretic responses to PE were inhibited by 5-MeU in SHRHNA only (P < 0.05).
Conclusion. The data suggest that, irrespective of the level of dietary sodium intake, α1A-ARs are the functional subtypes in SHR. However, there also appears to be a role for α1A-AR in mediating enhanced renal cortical vascular resistance, augmented tubular Na+ and water reabsorption in SHRHNa rats.
Streszczenie
Wprowadzenie. Zwiększone spożycie sodu nasila wzrost ciśnienia krwi u szczurów z samoistnym nadciśnieniem tętniczym (SHR), które jest związane z nasileniem oporu naczyniowego nerek i wchłanianiem zwrotnym płynu. Nerwy współczulne nerek wywierają swoje działanie przez α1-adrenoreceptory (α1-AR), a α1A jest głównym podtypem w regulacji hemodynamiki nerek i czynności wydalniczych.
Cel pracy. Zbadanie, czy wkład α1A-AR do regulacji zwężenia naczyń nerek i czynności wydalniczych został zwiększony u szczurów z samoistnym nadciśnieniem tętniczym spożywających dużo sodu.
Materiał i metody. Szczury otrzymywały albo wodę (SHRNNa), albo sól fizjologiczną (SHRHNa) przez sześć tygodni. Badanie w klatkach metabolicznych przeprowadzono po doświadczeniu ostrym w celu zbadania odpowiedzi zwężającej naczynia i wydalniczej nerek na katecholaminy, a mianowicie noradrenalinę (NA), fenylefrynę (PE) i metoksaminę (ME) w obecności i braku leku blokującego α1A-AR i 5-methylurapidilu (5-Meu).
Wyniki. Dzienne spożycie wody i wydalanie moczu było większe w grupie SHRHNa (p < 0,05 vs SHRNNa). Odpowiedź korowa naczyń nerek na NA, PE i ME była większa w grupie SHRHNa (p < 0,05 vs SHRNNa), a największy rezultat zaobserwowano pod wpływem ME. Śródnerkowy wlew PE wywołał antydiurezę i antynatriurezę. Niezależnie od spożycia sodu, 5-Meu wyraźnie ograniczył zwężenie naczyń krwionośnych wywołane adrenergicznie u szczurów z samoistnym nadciśnieniem tętniczym, a antynatriuretyczne i antydiuretyczne odpowiedzi na PE były hamowane przez 5-Meu tylko w grupie SHRHNA (P < 0,05).
Wnioski. Dane wskazują, że niezależnie od poziomu spożycia sodu, α1A-AR są czynnościowym podtypem u szczurów z samoistnym nadciśnieniem tętniczym. Wydaje się też, że swoją rolę spełnia α1A-AR w mediacji zwiększenia oporu naczyń nerkowych warstwy korowej, wzbogacania cewkowego Na+ i reabsorpcji wody u szczurów SHRHNa.
Key words
high salt, α1A-adrenoceptors, kidney, SHR
Słowa kluczowe
duże stężenie soli, α1A-adrenoreceptory, nerka, szczury z samoistnym nadciśnieniem tętniczym
References (24)
- Barsanti JA, Pillsbury HR, Freis ED: Enhanced salt toxicity in the spontaneously hypertensive rat. Proc Soc Exp Biol Med 1971, 136, 565–568.
- Louis WJ, Tabei R, Spector S: Effects of sodium intake on inherited hypertension in the rat. Lancet 1971, 2, 1283–1286.
- Saiz J, Lara B, Torres A, Sanchez A: Hypertensinogenic factors and renal α-adrenoceptors in young SHR and WKY rats. Life Sci 1987, 41, 2261–2268
- Michel MC, Brodde OE, Insel PA: Peripheral adrenergic receptors in hypertension. Hypertension 1990, 16,107–120.
- Tanoue A, Koba M, Miyawaki S, Koshimizu T-A, Hosoda C, Oshikawa S, Tsujimoto G: Role of the alpha1Dadrenegric Receptor in the development of salt-induced hypertension. Hypertension 2002, 40(1), 101–106.
- Dietz R, Schomig A, Rascher W, Strasser R, Luth JB, Ganten U, Kubler W: Contribution of the sympathetic nervous system to the hypertensive effect of a high sodium diet in stroke-prone spontaneously hypertensive rats. Hypertension 1982, 4(6), 773–781.
- Mark AL, Lawton WJ, Abboud FM, Fitz AE, Connor WE, Heistad DD: Effects of high and low sodium intake on arterial pressure and forearm vasular resistance in borderline hypertension. A preliminary report. Circ Res 1975, 36(6), 194–198.
- Kazi RN, Munavvar AS, Abdullah NA, Khan AH, Johns EJ: Influence of high dietary sodium intake on the functional subtypes of α1-adrenoceptors in the renal cortical vasculature of Wistar–Kyoto rats. Auton Autacoid Pharmacol 2009, 29(1–2), 25–31.
- DiBona GF, Kopp UC: Neural control of renal function. Physiol Rev 1997, 77(1), 75–197.
- Liu F, Nesbitt T, Drezner MK, Friedman PA, Gesek FA: Proximal nephron Na+/H+ exchange is regulated by alpha 1Aand alpha 1B-adrenergic receptor subtypes. Mol Pharmacol 1997, 52(6), 1010–1018.
- Clarke DE, Vemont RL, Blue DR, JR: Vascular α1-adrenoceptors in rat kidney: agonists and antagonists [prazosin, WB 4101, (+) niguldipine] characterization. Eur J Pharmacol 1990, 183, 733.
- Armenia A Sattar MA, Abdullah NA, Khan MA Johns EJ: Functional subtypes of renal alpha1-adrenoceptor in diabetic and non-diabetic 2K1C Goldblatt renovascular hypertension. Acta Pharmacol Sinica 2008, 29(5), 564–72.
- Sattar MA, Johns EJ: Evidence for an α1-adrenoceptor subtype mediating adrenergic vasoconstriction in wistar normotensive and stroke-prone spontaneously hypertensive rat kidney. J Cardiovasc Pharmacol 1994, 23(2), 232–239.
- Sattar MA, Johns EJ: The α1-adrenoceptor subtypes mediating adrenergically mediated antidiuresis and antinatriuresis in the Wistar and stroke-prone spontaneously hypertensive rats. Eur J Pharmacol 1995, 294, 727–736.
- Valin Reja, Ann K. Goodchild and Paul M. Pilowsky: Catecholamine-Related Gene Expression Correlates With Blood Pressures in SHR. Hypertension 2002, 40, 342–347.
- Bojesen: A method for determination of inulin in plasma and urine. Acta Physiol Scand 1952, 142, Suppl. 266, 275.
- Johns EJ, Manitius J: An investigation into the alpha-adrenoceptor mediating renal nerve-induced calcium reabsorption by the rat kidney. Br J Pharmacol 1986, 89(1), 91–97.
- DiBona GF, Sawin LL: Effect of renal nerve stimulation on NaCl and H2O transport in Henle’s loop of the rat. Am J Physiol Renal Physiol 1982, 243(6), F576–580.
- Cooper CL, Malik KU: Prostaglandin synthesis and renal vasoconstriction elicited by adrenergic stimuli are linked to activation of alpha-1 adrenergic receptors in the isolated rat kidney. J Pharmacol Exp Ther 1985, 233(1), 24–31.
- Blue DR, Jr Vimont RL, Clarke DE: Evidence for a noradrenergic innervation to alpha 1A-adrenoceptors in rat kidney. Br J Pharmacol 1992, 107(2), 414–417.
- Egan, B. M: Vascular reactivity, sympathetic tone, and stress. In: E. H. Johnson, W. D. Gentry, & S. Julius (Eds.), Personality, elevated blood pressure and essential hypertension. Washington, DC: Hemisphere. 1992; 231–255.
- Takeshita A, Mark AL: Mechanisms of vasoconstrictor response to high sodium intake in spontaneously hypertensive rats. Clin Res 1977, 25, 257A.
- Takata Y, Kato H: Adrenoceptors in SHR: alterations in binding characteristics and intracellular signal transduction pathways. Life Sci 1996, 58(2), 91–106.
- DiBona G: Neural control of renal function: role of renal alpha adrenoceptors. J Cardiovasc Pharmacol 1985, 7 (Suppl 8), S18–23.


