Vitamin D was Superior to Omega-3 as a Simvastatin Adjuvant in Improving Blood Lipids and Atherogenic Index in Type-I Dyslipidemic Rats.

Objectives: Adjuvant therapy is often used to optimize the antihyperlipidemic effect of simvastatin. Omega-3 and vitamin D supplementation are recommended as adjuvant therapies to low-intensity statins. This study aimed to compare the effects of vitamin D and omega-3 as adjuvant therapy to simvastatin to improve the lipid profiles and atherogenic index of plasma (AIP) in type-I dyslipidemic rats. Materials and Methods: Thirty-six male rats were randomized and divided into six groups: healthy control, dyslipidemic rats with no treatment, and dyslipidemic rats treated with either low-dose simvastatin only or omega-3 or vitamin D at low and high doses. Dyslipidemia was induced with high-fat diets for four weeks, followed by treatment for the next two weeks. Blood samples were withdrawn before and after simvastatin treatment. In addition, aspartate transaminase (AST) and alanine transaminase (ALT) levels were analyzed to assess liver function. Results: Administration of a high-fat diet-induced type 1 dyslipidemia and increased ALT levels (p < 0.05). Treatment with low-dose simvastatin did not significantly improve triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDLc) or non-HDLc levels. When combined with a high-dose vitamin D, simvastatin significantly reduced TG and increased HDLc levels (p < 0.05), thereby improving AIP levels. This improvement was not observed in rats treated with omega-3 or vitamin D at a lower dose. Conclusion: We concluded that high-dose vitamin D as an adjuvant to simvastatin therapy was superior to omega-3 in improving TG, HDL, and AIP levels. High-dose vitamin D also improved ALT levels in type-I dyslipidemic rats. This result may be translated in clinics to reduce the risk of coronary syndrome in patients with type-I dyslipidemia.

Analysis of antioxidant activity on cocktail honey products as female pre-conception supplements.

OBJECTIVE: Cocktail honey is derived from a mixture of honey (trigona sp.), bee bread, and homogeneous royal jelly. The material has a phenolic content rich in antioxidants that are beneficial for women's reproductive health, especially for pre-conception, because it can suppress the content of free radicals in the body. Antioxidants are useful to overcome oxidative damage due to free radicals in the body that prevent various diseases from increasing fertility during pre-conception. METHOD: This study used the DPPH (2,2-diphenyl-1-picrylhydrazyl) test method using UV-vis spectrophotometry to express the value of free radical reduction activity as IC50 (inhibitory concentration) values. RESULTS: The DPPH test on cocktail honey products obtained an average yield of 4577.7µg/mL, which was included in the product category was very weak in the antioxidant activity content. CONCLUSION: The content contained in the honey cocktail contains weak bioactive content by assessing the antioxidant content using DPPH. The difference in the results of antioxidant activity tests using DPPH is caused by the test method and the conditions used in processing, homogeneous ingredients, solvent volume, extraction time, temperature, and pressure in product management.

Ginger honey affects cortisol, estrogen and glutathione levels; preliminary study to target preconceptional women.

OBJECTIVE: This study was aimed to determine the effect of ginger honey supplementation on cortisol, glutathione, and estrogen levels. The study was conducted on mice that had not yet experienced conception, and prior stress induction was carried out so that they could be continued for human trials at the preconception stage and subjects who experienced mild stress. METHOD: It was an in vivo study, pretest-posttest control group design. The sample of this study was 2-3 months female Balb/c mice, divided into negative control and ginger honey intervention as much as 28mg/20g BW for 14 days-the ELISA method used to examine cortisol hormone, glutathione levels, and estrogen levels. The mice chosen were those that had never experienced conception, and before the intervention, swimming activities were carried out on the mice until they showed symptoms of stress. RESULTS: Results show 42mg/20g BW of ginger honey administration for 14 days increased 1.892 ng/dl of cortisol (p = 0.165), increased 2.438 ng/dl of glutathione (p=0.002), and also increased 22.754ng/ml estrogen levels in induced stress Balb/c female mice (p=0.001). CONCLUSION: Ginger honey did not affect reducing cortisol levels but increasing glutathione and estrogen levels significantly. Ginger honey supplements are the potential to use as complementary therapies.

Effect of royal jelly to deal with stress oxidative in preconception women: A literature review.

INTRODUCTION: Oxidative stress that occurs in preconception women can disrupt the reproductive system to cause infertility. The antioxidants contained in royal jelly can overcome oxidative stress due to low antioxidants in the body. The purpose of this study is to examine studies of the content of royal jelly, antioxidant activity, and the effectiveness of royal jelly in dealing with oxidative stress in preconception women. METHOD: This research method is an electronic database search using keywords according to questions in research from the online library PubMed, content science, and Science Direct. RESULT: a study review conducted in 6 research journals stated that the use of royal jelly as a supplement containing 10-hydroxy-2-decanoic (10-HDA) increases glutathione levels, as well as lipid peroxidation inhibitors. CONCLUSION: The effectiveness of royal jelly to overcome oxidative stress in preconception women can be assessed from the content of royal jelly and antioxidant activity that can increase the glutathione levels and inhibit increased lipid peroxidation, which is a sign of oxidative stress.

The influence of macronutrient intake, stress and prostaglandin levels (pgf2α) of urine with the incidence of dysmenorrhea in adolescents.

OBJECTIVES: This study aimed to analyze the influence of macronutrient intake, stress, and prostaglandin levels (pgf2α) on adolescent dysmenorrhea incidence. METHOD: This type of study is observational analytic with a cohort study draft done in January-March 2020 at High junior school 21 Makassar. Respondents in this study were grade X and XI students divided into 64 teenagers who had dysmenorrhea and 64 adolescents who did not experience Dysmenrhea. The criteria of the respondent in this study were the reproductive age, already experiencing menstruation, knowing the time and date of menstruation, menstrual cycles were regular, and willing to be respondents. The study used Menstrual Symptoms Questionnaire (MSQ) and used an ultrasonography (ultrasound) examination to perform the sample cervical. Food recall 24 hours to assess the intake of macronutrients, Depression Anxiety Stress Scales (DASS 42) to measure stress levels, and an examination of urine prostaglandin levels using the method Enzyme-Linked Immunosorbent Assay (ELISA). Urine intake is carried out on the second day as much as 2-5cc. Data were analyzed by the Chi-square test and logistics regression backward. RESULT: A multivariate analysis showed a variable that strongly affects dysmenorrhea is stress with the value p=0.000 and the level of prostaglandins with p-value=0.003 compared to other variables. CONCLUSION: Stress and prostaglandin levels significantly affect the occurrence of dysmenorrhea in adolescents.

The use of aromatherapy in primary dysmenorrhea.

OBJECTIVE: The purpose of this review is to determine the use of aromatherapy in primary dysmenorrhea. METHOD: This is a literature review by searching article databases through Google Scholar, PubMed, ScienceDirect, Microsoft Academic, ProQuest, Semantic Scholar. The selection period for article publication is from 2015 to 2021. A total of 96 articles were obtained, and 30 articles could be entered according to the inclusion criteria. RESULTS: Thirty articles were analyzed, it is shown that aromatherapy effectively reduces the intensity of primary dysmenorrheal pain. The sample size of the 30 articles varied from 16 samples to 200 research samples, and the research design used experiments, clinical trials, and ex vivo, in vivo, and in vitro studies. CONCLUSION: Aromatherapy is an effective alternative intervention that can be used to reduce the intensity of primary dysmenorrhea pain.

Exercise adaptations and TGF-ß1 levels in recreational cyclists.

BACKGROUND: Cycling is a physical exercise that is widely performed to improve physical fitness. Regular physical exercise will lead to adaptations to exercise. This adaptation is useful in suppressing the production of reactive oxygen stress (ROS) generated in response to cellular metabolism that uses oxygen. Transforming growth factor beta-1 (TGF-ß1) plays a role in increasing the production of ROS, thus, when the concentration is low, it would lead to an improvement in physical fitness. This study aims to compare levels of TGF-ß1 between recreational cyclists and sedentary groups. In addition, this research also compares several other parameters, which are fasting blood sugar levels and lipid profiles (triglycerides, total cholesterol, HDL cholesterol, and LDL cholesterol) between cyclists and sedentaries. METHODS: This was an observational analytical study with a cross-sectional design. The research subjects consisted of 2 groups, each consisting of 21 participants, namely the recreational cyclist and the sedentary group. Anthropometric examinations were carried out, including body weight, height, body mass index, waist circumference, and body fat percentage. Fasting blood glucose concentration and lipid profile (Triglyceride - TG, Total Cholesterol - Total C, HDL Cholesterol - HDL-C, and LDL Cholesterol - LDL-C) were determined by the enzymatic colorimetric methods, and TGF-ß1 levels were determined using the fluorescence of specific antibodies for TGF-ß1 (pg/ml) using ELISA method. Statistical analysis was performed using IBM SPSS v. 25. RESULTS: The anthropometric variables, other than body height, did not differ significantly between the two groups, so did the fasting blood glucose concentration. Nevertheless, the lipid profile (TG, Total C, HDL-C and LDL-C) were found to be significantly better in the cyclist group (p < 0.05).The mean level of TGF-ß1 in recreational cyclists was 8, 908.48 pg/ml, lower than the control group, 10, 229.28 pg/ml. The results of the unpaired t-test showed significant mean differences between the two groups, (p = 0.001; p < 0.05). CONCLUSION: The levels of TGF-ß1 in the recreational cyclist group were lower than the sedentary group. Regular physical exercise will trigger exercise adaptations that can suppress latent TGF-ß1 activation.

Analysis of antioxidant activity on cocktail honey products as female pre-conception supplements

Objective: Cocktail honey is derived from a mixture of honey (trigona sp.), bee bread, and homogeneous royal jelly. The material has a phenolic content rich in antioxidants that are beneficial for women's reproductive health, especially for pre-conception, because it can suppress the content of free radicals in the body. Antioxidants are useful to overcome oxidative damage due to free radicals in the body that prevent various diseases from increasing fertility during pre-conception. Method: This study used the DPPH (2,2-diphenyl-1-picrylhydrazyl) test method using UV–vis spectrophotometry to express the value of free radical reduction activity as IC50 (inhibitory concentration) values. Results: The DPPH test on cocktail honey products obtained an average yield of 4577.7 μg/mL, which was included in the product category was very weak in the antioxidant activity content. Conclusion: The content contained in the honey cocktail contains weak bioactive content by assessing the antioxidant content using DPPH. The difference in the results of antioxidant activity tests using DPPH is caused by the test method and the conditions used in processing, homogeneous ingredients, solvent volume, extraction time, temperature, and pressure in product management. (AU)

Ginger honey affects cortisol, estrogen and glutathione levels; preliminary study to target preconceptional women

Objective: This study was aimed to determine the effect of ginger honey supplementation on cortisol, glutathione, and estrogen levels. The study was conducted on mice that had not yet experienced conception, and prior stress induction was carried out so that they could be continued for human trials at the preconception stage and subjects who experienced mild stress. Method: It was an in vivo study, pretest–posttest control group design. The sample of this study was 2–3 months female Balb/c mice, divided into negative control and ginger honey intervention as much as 28 mg/20 g BW for 14 days—the ELISA method used to examine cortisol hormone, glutathione levels, and estrogen levels. The mice chosen were those that had never experienced conception, and before the intervention, swimming activities were carried out on the mice until they showed symptoms of stress. Results: Results show 42 mg/20 g BW of ginger honey administration for 14 days increased 1.892 ng/dl of cortisol (p = 0.165), increased 2.438 ng/dl of glutathione (p = 0.002), and also increased 22.754 ng/ml estrogen levels in induced stress Balb/c female mice (p = 0.001). Conclusion: Ginger honey did not affect reducing cortisol levels but increasing glutathione and estrogen levels significantly. Ginger honey supplements are the potential to use as complementary therapies. (AU)

Effect of royal jelly to deal with stress oxidative in preconception women: A literature review

Introduction: Oxidative stress that occurs in preconception women can disrupt the reproductive system to cause infertility. The antioxidants contained in royal jelly can overcome oxidative stress due to low antioxidants in the body. The purpose of this study is to examine studies of the content of royal jelly, antioxidant activity, and the effectiveness of royal jelly in dealing with oxidative stress in preconception women. Method: This research method is an electronic database search using keywords according to questions in research from the online library PubMed, content science, and Science Direct. Result: a study review conducted in 6 research journals stated that the use of royal jelly as a supplement containing 10-hydroxy-2-decanoic (10-HDA) increases glutathione levels, as well as lipid peroxidation inhibitors. Conclusion: The effectiveness of royal jelly to overcome oxidative stress in preconception women can be assessed from the content of royal jelly and antioxidant activity that can increase the glutathione levels and inhibit increased lipid peroxidation, which is a sign of oxidative stress. (AU)

The influence of macronutrient intake, stress and prostaglandin levels (pgf2a) of urine with the incidence of dysmenorrhea in adolescents

Objectives: This study aimed to analyze the influence of macronutrient intake, stress, and prostaglandin levels (pgf2α) on adolescent dysmenorrhea incidence. Method: This type of study is observational analytic with a cohort study draft done in January–March 2020 at High junior school 21 Makassar. Respondents in this study were grade X and XI students divided into 64 teenagers who had dysmenorrhea and 64 adolescents who did not experience Dysmenrhea. The criteria of the respondent in this study were the reproductive age, already experiencing menstruation, knowing the time and date of menstruation, menstrual cycles were regular, and willing to be respondents. The study used Menstrual Symptoms Questionnaire (MSQ) and used an ultrasonography (ultrasound) examination to perform the sample cervical. Food recall 24 hours to assess the intake of macronutrients, Depression Anxiety Stress Scales (DASS 42) to measure stress levels, and an examination of urine prostaglandin levels using the method Enzyme-Linked Immunosorbent Assay (ELISA). Urine intake is carried out on the second day as much as 2–5 cc. Data were analyzed by the Chi-square test and logistics regression backward. Result: A multivariate analysis showed a variable that strongly affects dysmenorrhea is stress with the value p = 0.000 and the level of prostaglandins with p-value = 0.003 compared to other variables. Conclusion: Stress and prostaglandin levels significantly affect the occurrence of dysmenorrhea in adolescents. (AU)

The use of aromatherapy in primary dysmenorrhea

Objective: The purpose of this review is to determine the use of aromatherapy in primary dysmenorrhea. Method: This is a literature review by searching article databases through Google Scholar, PubMed, ScienceDirect, Microsoft Academic, ProQuest, Semantic Scholar. The selection period for article publication is from 2015 to 2021. A total of 96 articles were obtained, and 30 articles could be entered according to the inclusion criteria. Results: Thirty articles were analyzed, it is shown that aromatherapy effectively reduces the intensity of primary dysmenorrheal pain. The sample size of the 30 articles varied from 16 samples to 200 research samples, and the research design used experiments, clinical trials, and ex vivo, in vivo, and in vitro studies. Conclusion: Aromatherapy is an effective alternative intervention that can be used to reduce the intensity of primary dysmenorrhea pain. (AU)

Long-Term Ketogenic Diet Induces Metabolic Acidosis, Anemia, and Oxidative Stress in Healthy Wistar Rats.

BACKGROUND: Ketogenic diet has been used as supportive therapy in a range of conditions including epilepsy, diabetes mellitus, and cancer. OBJECTIVE: This study aimed to investigate the effects of long-term consumption of ketogenic diet on blood gas, hematological profiles, organ functions, and superoxide dismutase level in a rat model. MATERIALS AND METHODS: Fifteen male Wistar rats were divided into control (n = 8) and ketogenic (n = 7) groups. Controls received standard diet contained 52.20% of carbohydrates, 7.00% fat, and 15.25% protein; meanwhile, the ketogenic group received a high-fat-low-carbohydrate diet which contained 5.66% of carbohydrate, 86.19% fat, and 8.15% protein. All rats were caged individually and received 30g of either standard or high-fat-low-carbohydrate pellets. The experiment was carried out for 60 days before the blood samples were taken and analyzed to obtain blood gas, cell counts, organ biomarkers, and plasma antioxidant superoxide dismutase (SOD) levels. RESULTS: The rats subjected to ketogenic diet experienced a marked decrease in body weight, blood sugar, and increased blood ketones (p < 0.05). The average blood pH was 7.36 ± 0.02 and base excess was -5.57 ± 2.39 mOsm/L, which were significantly lower than controls (p < 0.05). Hematological analysis showed significantly lower erythrocyte, hemoglobin, and hematocrit levels. No significant changes were found in alanine aminotransferase, aspartate aminotransferase, urea, and creatinine levels, indicating normal liver and kidney functions. Nevertheless, plasma SOD level significantly reduced with ketogenic diet. CONCLUSION: Long-term ketogenic diet induces metabolic acidosis, anemia, and reduced antioxidant enzyme level in rats following 60 days of consuming high-fat-low-carbohydrate diet.

The rise of circulatory endothelin (ET)-1 and endothelin receptors (ETA, ETB) expression in kidney of obese wistar rat.

BACKGROUND: Endothelin (ET)-1, a circulatory protein, and its receptors (ETA and ETB) in various organs were reported to play a pivotal role in many diseases, including obesity. However, the changes of ETA and ETB expression in ventricle and kidney in obesity was less reported. The study is designed to observe the level of circulatory ET-1 and expression of ETA/ETB in ventricle and kidney of obese, as compared to non-obese, Wistar rats. METHODS: Groups of obese 14 and 34 weeks Wistar rats were compared to non-obese controls at similar ages. The obesity status was achieved by feeding the with high calories protein diet CP 551 + milk powder, while the control group was fed with a standard calorie protein AD II diet. The concentration of circulatory ET-1, ETA and ETB of ventricle and kidney were measured by Enzyme Linked Immunosorbent Assay (ELISA) technique after the termination of both groups at 14th and 24th weeks. RESULTS: The level of circulatory ET-1, expression of ETA and ETB in kidney, and LDL of obese rats were significantly higher than control rats (T-Test, P<0.05) in the elder groups, while no differences of the ETA and ETB were found in the ventricle. No differences of the levels of circulatory ET-1, ETA and ETB expression were found between obese and control groups of younger rats (P>0.05). HDL levels were under normal value for both groups. CONCLUSION: Obesity in elder obese rats leads to dysregulation of kidney vessels through activity of ET-1 and ETA/ETB.

Adenosine and lidocaine (AL) combination dilates intimally damaged rat thoracic aortic rings and guinea pig mesenteric arteries: possible significance to cardiac surgery.

New pharmacotherapies are required to improve vessel graft protection and prevent vasoconstriction and spasm in CABG surgery. Previously we have studied adenosine (A) and lidocaine (L) relaxation in rat aortic rings, and reported a possible crosstalk between L relaxation and adenosine A2a receptor inhibition. The aim of the present study was to examine the effect of AL combination compared to A and L alone on relaxation in intact and denuded rat aortic rings and in guinea-pig pressurized mesenteric arterial segments. Aortic rings were harvested from Sprague-Dawley rats and equilibrated in an organ bath containing modified Krebs-Henseleit (KH) solution, pH 7.4, 37°C. Rings were pre-contracted sub-maximally with 0.3 µM norepinephrine, and the effects of increasing AL, A or L (up to 1.0 mM) were examined in intact and denuded rings. Mesenteric artery segments were isolated from guinea-pigs and mounted in an arteriograph containing KH solution and pressurised to 60 mmHg. Arteries were preconstricted with 10-8 M vasopressin and AL, A, or L was administered luminally or abluminally. Diameters were measured using video-microscopy. We report in intact rat aortic rings, AL increased relaxation from 21 to 100% (0.1-1.0 mM) and relaxation was endothelium-independent. Adenosine alone was also a potent relaxant of aortic rings but, unlike AL relaxation, it was partially endothelium-dependent. In intact mesenteric artery segments, increasing luminal AL produced a potent endothelium-independent dilation (up to 90%). Adenosine dilation was endothelium-independent but not lidocaine, which produced 33% dilation only after endothelial removal. Extra-luminal AL and A led to 76% and 80% dilationin intact segments respectively, whereas L resulted in constriction (10-17%). In conclusion, we show that AL can dilate aortic rings and mesenteric artery segments by up to 90% regardless of whether the endothelium is intact. We discuss the potential translational significance of AL to improve conduit protection in cardiac surgery, and other major surgeries.

The Adenosine Hypothesis Revisited: Modulation of Coupling between Myocardial Perfusion and Arterial Compliance.

For over four decades the thoracic aortic ring model has become one of the most widely used methods to study vascular reactivity and electromechanical coupling. A question that is rarely asked, however, is what function does a drug-mediated relaxation (or contraction) in this model serve in the intact system? The physiological significance of adenosine relaxation in rings isolated from large elastic conduit arteries from a wide range of species remains largely unknown. We propose that adenosine relaxation increases aortic compliance in acute stress states and facilitates ventricular-arterial (VA) coupling, and thereby links compliance and coronary artery perfusion to myocardial energy metabolism. In 1963 Berne argued that adenosine acts as a local negative feedback regulator between oxygen supply and demand in the heart during hypoxic/ischemic stress. The adenosine VA coupling hypothesis extends and enhances Berne's "adenosine hypothesis" from a local regulatory scheme in the heart to include conduit arterial function. In multicellular organisms, evolution may have selected adenosine, nitric oxide, and other vascular mediators, to modulate VA coupling for optimal transfer of oxygen (and nutrients) from the lung, heart, large conduit arteries, arterioles and capillaries to respiring mitochondria. Finally, a discussion of the potential clinical significance of adenosine modulation of VA coupling is extended to vascular aging and disease, including hypertension, diabetes, obesity, coronary artery disease and heart failure.

Lidocaine relaxation in isolated rat aortic rings is enhanced by endothelial removal: possible role of Kv, KATP channels and A2a receptor crosstalk.

BACKGROUND: Lidocaine is an approved local anesthetic and Class 1B antiarrhythmic with a number of ancillary properties. Our aim was to investigate lidocaine's vasoreactivity properties in intact versus denuded rat thoracic aortic rings, and the effect of inhibitors of nitric oxide (NO), prostenoids, voltage-dependent Kv and KATP channels, membrane Na+/K+ pump, and A2a and A2b receptors. METHODS: Aortic rings were harvested from adult male Sprague Dawley rats and equilibrated in an organ bath containing oxygenated, modified Krebs-Henseleit solution, pH 7.4, 37 °C. The rings were pre-contracted sub-maximally with 0.3 µM norepinephrine (NE), and the effect of increasing lidocaine concentrations was examined. Rings were tested for viability after each experiment with maximally dilating 100 µM papaverine. The drugs 4-aminopyridine (4-AP), glibenclamide, 5-hydroxydecanoate, ouabain, 8-(3-chlorostyryl) caffeine and PSB-0788 were examined. RESULTS: All drugs tested had no significant effect on basal tension. Lidocaine relaxation in intact rings was biphasic between 1 and 10 µM (Phase 1) and 10 and 1000 µM (Phase 2). Mechanical removal of the endothelium resulted in further relaxation, and at lower concentrations ring sensitivity (% relaxation per µM lidocaine) significantly increased 3.5 times compared to intact rings. The relaxing factor(s) responsible for enhancing ring relaxation did not appear to be NO- or prostacyclin-dependent, as L-NAME and indomethacin had little or no effect on intact ring relaxation. In denuded rings, lidocaine relaxation was completely abolished by Kv channel inhibition and significantly reduced by antagonists of the MitoKATP channel, and to a lesser extent the SarcKATP channel. Curiously, A2a subtype receptor antagonism significantly inhibited lidocaine relaxation above 100 µM, but not the A2b receptor. CONCLUSIONS: We show that lidocaine relaxation in rat thoracic aorta was biphasic and significantly enhanced by endothelial removal, which did not appear to be NO or prostacyclin dependent. The unknown factor(s) responsible for enhanced relaxation was significantly reduced by Kv inhibition, 5-HD inhibition, and A2a subtype inhibition indicating a potential role for crosstalk in lidocaine's vasoreactivity.

Adenosine relaxation in isolated rat aortic rings and possible roles of smooth muscle Kv channels, KATP channels and A2a receptors.

BACKGROUND: An area of ongoing controversy is the role adenosine to regulate vascular tone in conduit vessels that regulate compliance, and the role of nitric oxide (NO), potassium channels and receptor subtypes involved. The aim of our study was to investigate adenosine relaxation in rat thoracic aortic rings, and the effect of inhibitors of NO, prostanoids, Kv, KATP channels, and A2a and A2b receptors. METHODS: Aortic rings were freshly harvested from adult male Sprague Dawley rats and equilibrated in an organ bath containing oxygenated, modified Krebs-Henseleit solution, 11 mM glucose, pH 7.4, 37 °C. Isolated rings were pre-contracted sub-maximally with 0.3 µM norepinephrine (NE), and the effect of increasing concentrations of adenosine (1 to 1000 µM) were examined. The drugs L-NAME, indomethacin, 4-aminopyridine (4-AP), glibenclamide, 5-hydroxydecanoate, ouabain, 8-(3-chlorostyryl) caffeine and PSB-0788 were examined in intact and denuded rings. Rings were tested for viability after each experiment. RESULTS: Adenosine induced a dose-dependent, triphasic relaxation response, and the mechanical removal of the endothelium significantly deceased adenosine relaxation above 10 µM. Interestingly, endothelial removal significantly decreased the responsiveness (defined as % relaxation per µM adenosine) by two-thirds between 10 and 100 µM, but not in the lower (1-10 µM) or higher (>100 µM) ranges. In intact rings, L-NAME significantly reduced relaxation, but not indomethacin. Antagonists of voltage-dependent Kv (4-AP), sarcolemma KATP (glibenclamide) and mitochondrial KATP channels (5-HD) led to significant reductions in relaxation in both intact and denuded rings, with ouabain having little or no effect. Adenosine-induced relaxation appeared to involve the A2a receptor, but not the A2b subtype. CONCLUSIONS: It was concluded that adenosine relaxation in NE-precontracted rat aortic rings was triphasic and endothelium-dependent above 10 µM, and relaxation involved endothelial nitric oxide (not prostanoids) and a complex interplay between smooth muscle A2a subtype and voltage-dependent Kv, SarcKATP and MitoKATP channels. The possible in vivo significance of the regulation of arterial compliance to left ventricular function coupling is discussed.