Nanomaterial-Based Scaffolds for Tissue Engineering Applications: A Review on Graphene, Carbon Nanotubes and Nanocellulose

Nanoscale biomaterials have garnered immense interest in the scientific community in the recent decade. This review specifically focuses on the application of three nanomaterials, i.e., graphene and its derivatives (graphene oxide, reduced graphene oxide), carbon nanotubes (CNTs) and nanocellulose (cellulose nanocrystals or CNCs and cellulose nanofibers or CNFs), in regenerating different types of tissues, including skin, cartilage, nerve, muscle and bone. Their excellent inherent (and tunable) physical, chemical, mechanical, electrical, thermal and optical properties make them suitable for a wide range of biomedical applications, including but not limited to diagnostics, therapeutics, biosensing, bioimaging, drug and gene delivery, tissue engineering and regenerative medicine. A state-of-the-art literature review of composite tissue scaffolds fabricated using these nanomaterials is provided, including the unique physicochemical properties and mechanisms that induce cell adhesion, growth, and differentiation into specific tissues. In addition, in vitro and in vivo cytotoxic effects and biodegradation behavior of these nanomaterials are presented. We also discuss challenges and gaps that still exist and need to be addressed in future research before clinical translation of these promising nanomaterials can be realized in a safe, efficacious, and economical manner.

A Comparative Study on Aqueous Chitosan Solution and Various Submucosal Injection Fluids Using a Three-Dimensional Sensor

Background/Aims@#Chitosan, a natural polymer widely used in the biomaterials field, has been proposed as a potential submucosal injection solution. The purpose of this study was to compare the performance and efficacy of aqueous chitosan solution and commercialized submucosal injection fluids using a three-dimensional sensor and to evaluate the efficacy of the measured parameters. @*Methods@#Normal saline (0.9% NaCl), as a control, Eleview ® (Poloxamer 188), Blue Eye TM (0.4% hyaluronic acid), and aqueous chitosan solution (2.0%) were injected into the submucosa of porcine stomachs ex vivo. The mucosal elevation height, elevated surface area, and angle of the tangent of the submucosal fluid cushion were measured using a three-dimensional sensor. The rates of change for each variable were calculated, and the correlation between parameters was analyzed. Tissue specimens were stained with hematoxylin and eosin. @*Results@#All variables exhibited the highest values under chitosan injection. The mucosal elevation height rate of change differed significantly between normal saline and chitosan solution (p=0.024). The elevated surface area rates of change for normal saline and Eleview® were significantly different from those for TS-905 and chitosan solution (p=0.006 and p=0.009, respectively). Further, height, area, and angle showed a positive correlation (p<0.001). A histological examination revealed an even distribution of aqueous chitosan within the submucosa without tissue damage. @*Conclusions@#Aqueous chitosan was superior to normal saline and Eleview® and was noninferior to TS-905. A three-dimensional sensor and the measured parameters were effective and useful for evaluating the performance of submucosal fluids.

Allogeneic Fibrin Clot for Odontogenic/Cementogenic Differentiation of Human Dental Mesenchymal Stem Cells

BACKGROUND@#Fetal bovine serum is widely used as a growth supplement for cell culture medium; however, animalbornepathogens increase the risk of transmitting infectious agents. Platelet-rich fibrin is recently considered as a successfulalternative but leukocytes present limits to its allogeneic feasibility. The aim of this study was to explore the effects ofallogeneic fibrin clot (AFC) without leukocytes on inducing odontogenic/cementogenic differentiation of human dentalpulp stem cells (hDPSCs) and human periodontal ligament stem cells (hPDLSCs) in vitro and in vivo. @*METHODS@#AFC was prepared by high-speed centrifugation and leukocytes were almost removed, and AFC serum wasobtained through three freeze–thaw cycles. hDPSCs and hPDLSCs were treated with AFC serum to investigate theodontogenic or cementogenic associated markers by real-time polymerase chain reaction. hDPSCs were treated with AFCserum and placed inside of dentin canal, hPDLSCs were treated with AFC serum to wrap outside of dentin, the mixture wasthen transplanted into the subcutaneous of nude mice for 12 weeks. @*RESULTS@#AFC serum exhibited enough growth factors and cytokines to induce odontogenic/cementogenic differentiationof hDPSCs and hPDLSCs in vitro. Furthermore, AFC seurum could induce hDPSCs to differentiate into odontoblastslikecells and pulp-like tissues, and hPDLSCs to regenerate cementum-like tissues. @*CONCLUSION@#AFC could be an alternative safe source with growth factors for the expansion of human dental mesenchymalstem cells (hDMSCs).

Allogeneic Fibrin Clot for Odontogenic/Cementogenic Differentiation of Human Dental Mesenchymal Stem Cells

BACKGROUND@#Fetal bovine serum is widely used as a growth supplement for cell culture medium; however, animalbornepathogens increase the risk of transmitting infectious agents. Platelet-rich fibrin is recently considered as a successfulalternative but leukocytes present limits to its allogeneic feasibility. The aim of this study was to explore the effects ofallogeneic fibrin clot (AFC) without leukocytes on inducing odontogenic/cementogenic differentiation of human dentalpulp stem cells (hDPSCs) and human periodontal ligament stem cells (hPDLSCs) in vitro and in vivo. @*METHODS@#AFC was prepared by high-speed centrifugation and leukocytes were almost removed, and AFC serum wasobtained through three freeze–thaw cycles. hDPSCs and hPDLSCs were treated with AFC serum to investigate theodontogenic or cementogenic associated markers by real-time polymerase chain reaction. hDPSCs were treated with AFCserum and placed inside of dentin canal, hPDLSCs were treated with AFC serum to wrap outside of dentin, the mixture wasthen transplanted into the subcutaneous of nude mice for 12 weeks. @*RESULTS@#AFC serum exhibited enough growth factors and cytokines to induce odontogenic/cementogenic differentiationof hDPSCs and hPDLSCs in vitro. Furthermore, AFC seurum could induce hDPSCs to differentiate into odontoblastslikecells and pulp-like tissues, and hPDLSCs to regenerate cementum-like tissues. @*CONCLUSION@#AFC could be an alternative safe source with growth factors for the expansion of human dental mesenchymalstem cells (hDMSCs).

Severe Hypophosphatemia-Induced Acute Toxic-Metabolic Encephalopathy in Continuous Renal Replacement Therapy

Acute toxic-metabolic encephalopathy (TME) is an acute condition of global cerebral dysfunction in the absence of primary structural brain disease. Severe hypophosphatemia leads to muscle weakness and involves the diaphragm but hypophosphatemia-induced TME is very rare. Herein, we report the case of a 43-year-old woman with encephalopathy with severe hypophosphatemia during continuous renal replacement therapy. She presented with features of oliguric acute kidney injury on diabetic kidney disease due to volume depletion. At admission, her mental status was alert but gradually changed to stupor mentation during continuous renal replacement therapy. Her phosphate level was less than 0.41 mEq/L and Glasgow coma scale decreased from 15 to 5. After phosphate intravenous replacement and administration of phosphate-containing replacement solution, the phosphate level increased to 2.97 mEq/L and mental state returned to alert state. This case demonstrates that the level of phosphorus should be observed during continuous renal replacement therapy.

Successful Treatment of Invasive Gastric Mucormycosis in a Kidney Transplant Recipient / 대한이식학회지

Mucormycosis is an extremely rare but potentially life-threatening fungal infection. Gastrointestinal (GI) mucormycosis is very rare and occurs primarily in highly malnourished patients, especially in infants and children. A 55-year-old man with end-stage renal disease due to diabetic nephropathy, who had undergone deceased donor kidney transplantation 2 years prior, complained of abdominal pain and distension with a 3-day duration. Computed tomography revealed diffuse gastric wall thickening, and a huge amount of grey colored necrotic debris surrounded by erythematous erosive mucosa was observed at the antrum to upper body by GI endoscopy. The microscopic examination obtained from a GI endoscopic specimen demonstrated peptic detritus with numerous non-septate mucor hyphae in the mucosa and submucosa. Mucormycosis was diagnosed based on the clinical findings and morphological features. A total gastrectomy was performed and an antifungal agent was administered. A microscopic examination of the surgical specimen demonstrated invasive mucormycosis with numerous fungal hyphae with invasion into the mucosa to subserosa. The patient and graft were treated successfully by total gastrectomy and antifungal therapy.

Colonic Mucormycosis Mimicking Ischemic Colitis in Kidney Transplant Recipient / 대한이식학회지

Mucormycosis is an extremely rare but potentially life-threatening fungal infection. Mucormycosis of the gastrointestinal tract manifests with features similar to ischemic colitis. A 48-year-old man with end-stage renal disease due to diabetic nephropathy underwent deceased donor kidney transplantation. He complained of abdominal pain and distension on postoperative day 17. A computed tomography (CT) scan revealed symmetrical wall thickening of the ascending colon, which was consistent with ischemic colitis. However, a follow-up CT scan showed a localized wall-off colon perforation in the hepatic flexure and segmental mural gas in the ascending colon. Microscopic examination obtained from a surgical specimen demonstrated numerous fungal hyphae and spores in the mucosa and submucosa. A total colectomy was performed, but the patient died 36 days later due to multiple organ failure, despite antifungal agents. Clinicians should be informed about fungal infection, such as colonic mucormycosis mimicking ischemic colitis, in kidney transplant patients with diabetes mellitus, and treatment should be initiated at the earliest.

Cyclophosphamide therapy for secondary amyloidosis in a patient with juvenile idiopathic arthritis unresponsive to tumor necrosis factor α inhibitor therapy

No abstract available.

Direct vascular actions of quercetin in aorta from renal hypertensive rats

BACKGROUND: Chronic treatment with the dietary flavonoid quercetin is known to lower blood pressure and restore endothelial dysfunction in animal models of hypertension. This study investigated the direct effects of quercetin on vascular response in chronic 2-kidney, 1-clip (2K1C) renal hypertensive rats. The effects of antioxidant vitamin ascorbic acid on the vasoreactivity were also examined. METHODS: 2K1C renal hypertension was induced by clipping the left renal artery; age-matched rats that received sham treatment served as controls. Thoracic aortae were mounted in tissue baths for the measurement of isometric tension. RESULTS: Relaxant responses to acetylcholine were significantly attenuated in 2K1C rats in comparison with sham rats. Quercetin or ascorbic acid augmented acetylcholine-induced relaxation in 2K1C rats, whereas no significant differences were noted in sham rats. The relaxation response to sodium nitroprusside was comparable between 2K1C and sham rats, and sodium nitroprusside-induced relaxation was not altered by quercetin or ascorbic acid in either group. The contractile response to phenylephrine was significantly enhanced in 2K1C rats compared with sham rats. Phenylephrine-induced contraction was inhibited by pretreatment with quercetin or ascorbic acid in 2K1C rats, whereas neither chemical affected responses in sham rats. N(w)-nitro-L-arginine methyl ester markedly augmented the contractile response to phenylephrine in sham rats, whereas no significant differences were observed in 2K1C rats. Quercetin or ascorbic acid did not affect phenylephrine-induced contraction in the presence of N(w)-nitro-L-arginine methyl ester in either 2K1C or sham rats. CONCLUSION: Acute exposure to quercetin appears to improve endothelium-dependent relaxation and inhibit the contractile response, similar to the effect of ascorbic acid in 2K1C hypertension. These results partially explain the vascular beneficial effects of quercetin in renal hypertension.

Cutoff value of serum procalcitonin as a diagnostic biomarker of infection in end-stage renal disease patients

BACKGROUND/AIMS: Serum procalcitonin (PCT) levels are low in healthy individuals but are elevated in patients with a serious bacterial infection or sepsis. In this study, we examined the ability of serum PCT concentration to diagnose infections in end-stage renal disease (ESRD) patients, and sought to determine an appropriate threshold level. METHODS: Serum PCT levels were measured in ESRD patients on antibiotic therapy for a suspected bacterial infection (ESRD infection [iESRD] group, n = 21), and compared with those of ESRD patients on hemodialysis with no sign of infection (ESRD control [cESRD] group, n = 20). RESULTS: The mean serum PCT concentration of the iESRD group was significantly higher than in the cESRD group (2.95 +/- 3.67 ng/mL vs. 0.50 +/- 0.49 ng/mL, p = 0.006), but serum PCT concentrations did not correlate with severity of infection. The optimized threshold level derived for serum PCT was 0.75 ng/mL, rather than the currently used 0.5 ng/mL; this threshold demonstrated a sensitivity and specificity of 76.2% and 80.0% for infection and 100% and 60.6% for systemic inflammatory response syndrome, respectively, compared with the cutoff of 0.5 ng/mL. CONCLUSIONS: This study suggests that serum PCT at a cutoff value of 0.75 ng/mL is an appropriate indicator of infection in ESRD patients.

Congenital nephrogenic diabetes insipidus with end-stage renal disease

No abstract available.

Mechanisms of phytoestrogen biochanin A-induced vasorelaxation in renovascular hypertensive rats

BACKGROUND: The plant-derived estrogen biochanin A is known to cause vasodilation, but its mechanism of action in hypertension remains unclear. This study was undertaken to investigate the effects and mechanisms of biochanin A on the thoracic aorta in two-kidney, one clip (2K1C) renovascular hypertensive rats. METHODS: Hypertension was induced by clipping the left renal artery, and control age-matched rats were sham treated. Thoracic aortae were mounted in tissue baths to measure isometric tension. RESULTS: Biochanin A caused concentration-dependent relaxation in aortic rings from 2K1C hypertensive and sham-treated rats, which was greater in 2K1C rats than in sham rats. Biochanin A-induced relaxation was significantly attenuated by removing the endothelium in aortic rings from 2K1C rats, but not in sham rats. Nomega-Nitro-L-arginine methylester, a nitric oxide synthase inhibitor, or indomethacin, a cyclooxygenase inhibitor, did not affect the biochanin A-induced relaxation in aortic rings from 2K1C and sham rats. By contrast, treatment with glibenclamide, a selective inhibitor of adenosine triphosphate-sensitive K+ channels, ortetraethy-lammonium, an inhibitor of Ca2+-activated K+ channels, significantly reduced biochanin A-induced relaxation in aortic rings from both groups. However, 4-aminopyridine, a selective inhibitor of voltage-dependent K+ channels, inhibited the relaxation induced by biochanin A in 2K1C rats, whereas no significant differences were observed in sham rats. CONCLUSION: These results suggest that the enhanced relaxation caused by biochanin A in aortic rings from hypertensive rats is endothelium dependent. Vascular smooth muscle K+ channels may be involved in biochanin A-induced relaxation in aortae from hypertensive and normotensive rats. In addition, an endothelium-derived activation of voltage-dependent K+ channels contributes, at least in part, to the relaxant effect of biochanin A in renovascular hypertension.

Effects of oxidative stress on endothelial modulation of contractions in aorta from renal hypertensive rats

BACKGROUND: Endothelial dysfunction is linked to exaggerated production of superoxide anions. This study was conducted to examine the effects of oxidative stress on endothelial modulation of contractions in chronic two-kidney, one-clip (2K1C) renal hypertensive rats. METHODS: The 2K1C hypertension was induced by clipping the left renal artery; age-matched rats receiving sham treatment served as controls. Thoracic aortae were isolated and mounted in tissue baths for measurement of isometric tension. RESULTS: Norepinephrine-induced contraction was augmented by the removal of the endothelium, which was more pronounced in sham rats than in 2K1C rats. Nomega-nitro-L-arginine methyl ester, an inhibitor of nitric oxide production, had a similar augmenting effect. Vitamin C inhibited the contraction in aortic rings with intact endothelium from 2K1C rats but not from sham rats. The contraction was also suppressed by treatment with diphenyleneiodonium or apocynin, inhibitors of nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase, in the aortae with intact endothelium from 2K1C rats but not in those from sham rats. Superoxide anions generated by xanthine oxidase/hypoxanthine enhanced the contraction in the aortae with intact endothelium from sham rats, but had no effect in 2K1C rats. Enhanced contractile responses to norepinephrine by xanthine oxidase/hypoxanthine in sham rats were reversed by vitamin C. CONCLUSION: These results suggest that the effect on endothelial modulation of endothelium-derived nitric oxide is impaired in 2K1C hypertension. The impairment is, at least in part, related to increased production of superoxide anions by NADH/NADPH oxidase.

Endothelium-dependent vasodilation by ferulic acid in aorta from chronic renal hypertensive rats

BACKGROUND: Ferulic acid (FA) is a naturally occurring nutritional compound. Although it has been shown to have antihypertensive effects, its effects on vascular function have not been intensively established. The aim of this study was to assess the vasoreactivity of FA in chronic two-kidney, one-clip (2K1C) renal hypertensive rats. METHODS: Hypertension was induced in 2K1C rats by clipping the left renal artery and age-matched rats that received a sham treatment served as a control. Thoracic aortas were mounted in tissue baths to measure isometric tension. The effects of FA on vasodilatory responses were evaluated based on contractile responses induced by phenylephrine in the aortic rings obtained from both 2K1C and sham rats. Basal nitric oxide (NO) bioavailability in the aorta was determined by the contractile response induced by NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). RESULTS: FA induced concentration-dependent relaxation responses which were greater in 2K1C hypertensive rats than in sham-clipped control rats. This relaxation induced by FA was partially blocked by the removal of endothelium or by pretreating with L-NAME. L-NAME-induced contractile responses were augmented by FA in 2K1C rats, while no significant differences were noted in sham rats. FA improved acetylcholine-induced endothelium-dependent vasodilation in 2K1C rats, but not in sham rats. The simultaneous addition of hydroxyhydroquinone significantly inhibited the increase in acetylcholine-induced vasodilation by FA. CONCLUSION: These results suggest that FA restores endothelial function by altering the bioavailability of NO in 2K1C hypertensive rats. The results explain, in part, the mechanism underlying the vascular effects of FA in chronic renal hypertension.

The effect of intravenous ascorbic acid in hemodialysis patients with normoferritinemic anemia

BACKGROUND: Hemodialysis (HD) patients with functional iron deficiency often develop resistance to recombinant human erythropoietin (rhEPO). Recent studies have shown that intravenous ascorbic acid (IVAA) administration could override rhEPO resistance in HD patients. This study was undertaken to test the effects of IVAA in HD patients with normoferritinemic functional iron deficiency accompanied by EPO-hyporesponsive anemia. METHODS: Fifty-eight HD patients with normoferritinemic anemia (between 100 and 500 microg/L) were included and divided into the control (N=25) and IVAA (N=33) groups. IVAA patients received 500 mg of IVAA with each dialysis session for 3 months and an additional 4-month follow-up after the end of the therapy. RESULTS: Twenty patients had a response to IVAA with a significant increase in hemoglobin level (Hgb4>1.0 g/dL) and reduction of weekly rhEPO dosage compared with the control group after 3 months of treatment (P<0.05). Compared with non-responders, transferrin saturation (TSAT) was significantly decreased in the responders group (26+/-11 vs. 35+/-14%, P<0.05) on baseline data. There was a significant increase in serum iron and TSAT (baseline vs. 3 months, serum iron 57+/-22 vs. 108+/-22 microg/dL, TSAT 26+/-11 vs. 52+/-7%, P<0.05) and a decrease in serum ferritin (377+/-146 vs. 233+/-145 ng/mL, P<0.05) in the responders group (N=20), but no significant changes in the control and non-responders groups (N=13) at 3-month treatment. CONCLUSION: IVAA can be a potent and effective adjuvant therapy for HD patients with rhEPO-resistant normoferritinemic anemia. In addition, IVAA can reduce the dosage of rhEPO for anemia correction.

Direct Vascular Actions of Indapamide in Aorta from Renal Hypertensive Rats / 대한신장학회지

PURPOSE: Thiazide diuretics exert their hypotensive efficacy through a combined vasodilator and diuretic effect. The present study was conducted to assess the inhibitory effect of thiazide diuretic, hydrochlorothiazide, and the thiazide-like diuretics, indapamide and chlorthalidone on contractile responses to norepinephrine and arginine vasopressin in aortic rings from 2K1C renal hypertensive and sham-clipped normotensive rats. METHODS: 2K1C hypertension was made by clipping the left renal artery and age-matched control rats received a sham treatment. Changes in the tension of aortic ring preparations were measured isometrically. RESULTS: Indapamide inhibits the contractile responses to norepinephrine and vasopressin in aortic rings from 2K1C rats, while it did not modify in control rats. The inhibitory effect of indapamide was abolished by endothelium removal. Hydrochlorothiazide or chlorthalidone did not affect the vasoconstriction induced by norepinephrine and vasopressin either in sham or in 2K1C hypertensive rats. CONCLUSION: These results suggest that indapamide inhibits the contractile responses to norepinephrine and vasopressin via an endothelium-dependent mechanism in 2K1C renal hypertension.

The Role of Oxygen-Derived Free Radicals in Vascular Relaxations to Pinacidil in Renal Hypertensive Rats / 대한신장학회지

PURPOSE: Evidence has emerged that oxygen-derived free radicals may induce vascular relaxations via ATP-sensitive K+ (K(ATP)) channels and the level of free radicals is increased in animal models of hypertension. The present study was conducted to determine whether relaxations to an K(ATP) channel opener, pinacidil, are increased in the aorta from two-kidney, one clip (2K1C) hypertensive rats and whether free radial scavengers reduce these relaxations. METHODS: 2K1C hypertension was induced by clipping the left renal artery and age-matched control rats received a sham treatment. Rings of aortae without endothelium were suspended for isometric force recording. RESULTS: Relaxations to pinacidil (10(-8) to 10(-5) M), which are abolished by glibenclamide (10(-5) M), were augmented in the aorta from 2K1C rats, compared to those from control rats. In the aorta from 2K1C rats, catalase (1,200 U/mL), but neither superoxide dismutase (150 U/mL) nor deferoxamine (10(-4) M), reduced relaxations to pinacidil, whereas in the aorta from control rats, the free radical scavengers did not affect these relaxations. CONCLUSION: These results suggest that in 2K1C hypertension, vasorelaxation to an KATP channel opener is augmented and that hydrogen peroxide in smooth muscle cells may partly contribute to these relaxations.

A Case of Acute Fatty Liver of Pregnancy with Renal Subcapsular Hemorrhage / 대한신장학회지

Wunderlich syndrome is a spontaneous rupture of the kidney. It is a rare but potentially life-threatening event. The causes are tumor, vascular disease, infection and preeclampsia. Subcapsular hepatic and renal hematoma are rare complications of pregnancy associated with preeclampsia or HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Acute fatty liver of pregnancy (AFLP) is rare, but is a fatal complication of the third trimester of pregnancy. The clinical picture consists of liver failure with coagulopathy, encephalopathy and hypoglycemia. Early recognization of the disorder, rapid termination of pregnancy, and intensive supportive care have improved the prognosis. AFLP should be distinguished from HELLP syndrome. AFLP is usually not associated with renal subcapusular hemorrhage. In this report, we describe a 36-year-old nullipara with twin male fetus at 35 weeks of gestation who had developed renal subcapsular hemorrhage in AFLP.

Complete Recovery of Renal Function in Bilateral Renal Cortical Necrosis: A Case Report / 대한신장학회지

Acute bilateral renal cortical necrosis (BRCN) is a rare cause of renal failure. It has been reported that contrast-enhanced computed tomography provides characteristic findings of BRCN which correlates well with the histopathology making it an important non-invasive diagnostic modality during early phase of BRCN, improving survival rate and prognosis with early diagnosis and treatment. This report presents a case of 73-year old woman with BRCN due to hemolytic uremic syndrome. The patient recovered from anuria and showed complete recovery to normal renal function of her age and serum creatinine level after early initiation of hemodialysis. Furthermore, a normal radiologic finding of kidney was obtained after 52 days from onset of the disease by contrast-enhanced computed tomography. At present, she is preserved within the normal range renal function without renal replacement therapy.

Modulation of Baroreflexes in Hypertensive Rats / 대한신장학회지

PURPOSE: Baroreceptor reflex regulation has been shown to reset towards a higher blood pressure level. This study was designed to assess alterations of chronotropic baroreflexes in two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. METHODS: Arterial pressure and heart rate (HR) were monitored continuously during intravenous infusions of phenylephrine or sodium nitroprusside. Ensuing reflex HR responses during each drug infusion were determined in two ways: (a) at 10 s intervals (time analysis), and (b) with every 10 mmHg change in pressure (pressure analysis). RESULTS: Both pressor and depressor responses produced by phenylephrine or sodium nitroprusside were comparable between normotensive and hypertensive rats. Both reflex tachycardia and bradycardia were attenuated in 2K1C hypertensive rats as compared with normotensive rats, whereas no significant differences were shown in DOCA-salt hypertensive rats. CONCLUSION: These results indicate that chronotropic baroreflexes are impaired in 2K1C hypertensive rats, but not in DOCA-salt hypertensive rats.