Effects of Norepinephrine on Renal Cortical and Medullary Blood Flow in Atherosclerotic Rabbits

Abstract

Objective

The aim of this study was to explore the effect of norepinephrine (NE) on renal cortical and medullary blood flow in atherosclerotic rabbits without renal artery stenosis.

Methods

Atherosclerosis was induced in 21 New Zealand white rabbits by feeding them a cholesterol-rich diet for 16 weeks. Thirteen healthy New Zealand white rabbits were randomly selected as controls. After atherosclerosis induction, standard ultrasonography was performed to confirm that there was no plaque or accelerated flow at the origin of the renal artery. Contrast-enhanced ultrasound (CEUS) was performed at baseline and during intravenous injection of NE. The degree of contrast enhancement of renal cortex and medulla after the injection of contrast agents was quantified by calculating the enhanced intensity.

Results

The serum nitric oxide (NO) level in atherosclerotic rabbits was higher than that in healthy rabbits (299.6±152 vs. 136.5±49.5, P<0.001). The infusion of NE induced a significant increase in the systolic blood pressure (112±14 mmHg vs. 84±9 mmHg, P=0.016) and a significant decrease in the enhanced intensity in renal cortex (17.78±2.07 dB vs. 21.19±2.03 dB, P<0.001) and renal medulla (14.87±1.82 dB vs. 17.14±1.89 dB, P<0.001) during CEUS. However, the enhanced intensity in the cortex and medulla of healthy rabbits after NE infusion showed no significant difference from that at baseline.

Conclusion

NE may reduce renal cortical and medullary blood flow in atherosclerotic rabbits without renal artery stenosis, partly by reducing the serum NO level.

Keywords

norepinephrine / atherosclerosis / contrast-enhanced ultrasound / renal blood flow

References

[1] MotiejunaiteJ, AmarL, Vidal-PetiotE. Adrenergic receptors and cardiovascular effects of catecholamines. Ann Endocrinol (Paris), 2021, 82(3–4): 193-197

[2] ProfumoE, ButtariB, D’ArcangeloD, et al.. The Nutraceutical Dehydrozingerone and Its Dimer Counteract Inflammation- and Oxidative Stress-Induced Dysfunction of In Vitro Cultured Human Endothelial Cells: A Novel Perspective for the Prevention and Therapy of Atherosclerosis. Oxid Med Cell Longev, 2016, 2016: 1246485

[3] BerkenboomG, DepierreuxM, FontaineJ. The influence of atherosclerosis on the mechanical responses of human isolated coronary arteries to substance P, isoprenaline and noradrenaline. Br J Pharmacol, 1987, 92(1): 113-120

[4] WroblewskiT, WitanowskaA. The contractile response of the normal and atherosclerotic aortic strips to noradrenaline, and potassium ions. Acta Physiol Pol, 1982, 33(4): 353-360

[5] LiT, MaoY, ZhaoB, et al.. Value of contrast-enhanced ultrasound for diagnosis and follow-up of renal artery stenosis in patients with chronic kidney disease. Abdom Radiol (NY), 2022, 47(5): 1853-1861

[6] WangL, MohanC. Contrast-enhanced ultrasound: A promising method for renal microvascular perfusion evaluation. J Transl Int Med, 2016, 4(3): 104-108

[7] SunJ, LiuK, TangQY, et al.. Correlation between enhanced intensity of atherosclerotic plaque at contrast-enhanced ultrasonography and density of histological neovascularization. J Huazhong Univ Sci Technolog Med Sci, 2013, 33(3): 443-446

[8] SunJ, DengYB, LiuK, et al.. Effects of noradrenaline and adenosine triphosphate on the degree on contrast enhancement in a rabbit model of atherosclerosis during contrast-enhanced ultrasonography. Ultrasound Med Biol, 2014, 40(11): 2655-2661

[9] LiY, ChahalN, SeniorR, et al.. Reproducible Computer-Assisted Quantification of Myocardial Perfusion with Contrast-Enhanced Ultrasound. Ultrasound Med Biol, 2017, 43(10): 2235-2246

[10] Juárez-OrozcoLE, SzymanskiMK, HillegeHL, et al.. Imaging of cardiac and renal perfusion in a rat model with 13N-NH 3 micro-PET. Int J Cardiovasc Imaging, 2015, 31(1): 213-219

[11] SchumannJ, HenrichEC, StroblH. Inotropic agents and vasodilator strategies for the treatment of cardiogenic shock or low cardiac output syndrome. Cochrane Database Syst Rev, 2018, 1(1): CD009669

[12] SchneiderAG, GoodwinMD, SchellemanA, et al.. Contrast-enhanced ultrasonography to evaluate changes in renal cortical microcirculation induced by noradrenaline: a pilot study. Crit Care, 2014, 18(6): 653

[13] BurkeM, PabbidiMR, FarleyJ, et al.. Molecular mechanisms of renal blood flow autoregulation. Curr Vasc Pharmacol, 2014, 12(6): 845-858

[14] AndersonWP, KornerPI, SeligSE. Mechanisms involved in the renal responses to intravenous and renal artery infusions of noradrenaline in conscious dogs. J Physiol, 1981, 321: 21-30

[15] FerreiraMG, FontelesMC. Different classes of PAF-antagonists block norepinephrine-induced vascular escape and tachyphylaxis in the isolated rabbit kidney. Res Commun Mol Pathol Pharmacol, 1996, 94(2): 147-155

[16] MossNG, KoppleTE, ArendshorstWJ. Renal vasoconstriction by vasopressin V1a receptors is modulated by nitric oxide, prostanoids, and superoxide but not the ADP ribosyl cyclase CD38. Am J Physiol Renal Physiol, 2014, 306(10): F1143-1154

[17] WroblewskiTE, GrojecM. Vasomotor escape from noradrenaline in the renal, mesenteric and hindquarter vascular beds in spontaneously hypertensive rats (SHR). Acta Physiol Pol, 1984, 35(4): 324-329

[18] ChenJY, YeZX, WangXF, et al.. Nitric oxide bioavailability dysfunction involves in atherosclerosis. Biomed Pharmacother, 2018, 97: 423-428

[19] ArgerPH, SehgalCM, PughCR, et al.. Evaluation of change in blood flow by contrast-enhanced power Doppler imaging during norepinephrine-induced renal vasoconstriction. J Ultrasound Med, 1999, 18(12): 843-851

[20] EvansRG, MaddenAC, DentonKM. Diversity of responses of renal cortical and medullary blood flow to vasoconstrictors in conscious rabbits. Acta Physiol Scand, 2000, 169(4): 297-308

[21] CorreiaAG, MaddenAC, BergströmG, et al.. Effects of renal medullary and intravenous norepinephrine on renal antihypertensive function. Hypertension, 2000, 35(4): 965-970

[22] MukaiK, KudaY, ShibamotoT, et al.. Renal response to anaphylaxis in anesthetized rats and isolated perfused rat kidneys: roles of nitric oxide. J Physiol Sci, 2018, 68(5): 689-697

[23] KeQ, CostaM. Hypoxia-inducible factor-1 (HIF-1). Mol Pharmacol, 2006, 70(5): 1469-1480

[24] LeDouxD, AstizME, CarpatiCM, et al.. Effects of perfusion pressure on tissue perfusion in septic shock. Crit Care Med, 2000, 28(8): 2729-2732

[25] LenzT. Ischemic renal disease and renal artery stenosis. Internist (Berl), 2015, 56(3): 248-254

[26] SchoepeR, McQuillanS, ValsanD, et al.. Atherosclerotic Renal Artery Stenosis. Adv Exp Med Biol, 2017, 956: 209-213