Vasorelaxant effects of biochemical constituents of various medicinal plants and their benefits in diabetes.

Endothelial function plays a pivotal role in cardiovascular health, and dysfunction in this context diminishes vasorelaxation concomitant with endothelial activity. The nitric oxide-cyclic guanosine monophosphate pathway, prostacyclin-cyclic adenosine monophosphate pathway, inhibition of phosphodiesterase, and the opening of potassium channels, coupled with the reduction of calcium levels in the cell, constitute critical mechanisms governing vasorelaxation. Cardiovascular disease stands as a significant contributor to morbidity and mortality among individuals with diabetes, with adults afflicted by diabetes exhibiting a heightened cardiovascular risk compared to their non-diabetic counterparts. A plethora of medicinal plants, characterized by potent pharmacological effects and minimal side effects, holds promise in addressing these concerns. In this review, we delineate various medicinal plants and their respective biochemical constituents, showcasing concurrent vasorelaxant and anti-diabetic activities.

Rosa damascena Miller essential oil relaxes rat trachea via K<sub>V</sub> channels, K<sub>ATP</sub> channels, and BK<sub>Ca</sub> channels.

AIM/OBJECTIVE: This study aimed to investigate the effects of Rosa damascena Miller essential oil on rat tracheal smooth muscle contractility and the hypothesis that voltage-gated potassium (K<sub>V</sub>) channels, ATP-sensitive potassium (K<sub>ATP</sub>) channels, and large-conductance calcium-activated potassium (BK<sub>Ca</sub>) channels may have roles in these effects. METHODS: Isometric contraction-relaxation responses of tracheal rings were measured with an isolated tissue bath model. The steady contraction was induced with both 10<sup>-5</sup> M ACh and 60 mM KCl, and then the concentration-dependent responses of rose oil (0.1-100 µg/mL) were examined. The time-matched control (double distilled water) group was also formed. To evaluate the role of K<sub>V</sub>, K<sub>ATP</sub>, and BK<sub>Ca</sub> channels, tracheal rings were incubated with 4-AP (K<sub>V</sub> channel blocker), glibenclamide (K<sub>ATP</sub> channel blocker), TEA (BK<sub>Ca</sub> channel blocker), and iberiotoxin (selective BK<sub>Ca</sub> channel blocker). Also, a vehicle control group was formed for dimethyl sulfoxide (DMSO). RESULTS: Rose oil exerted the relaxant effects in tracheal rings pre-contracted with both ACh and KCl at concentrations of 1, 10, and 100 µg/mL (p < 0.05). Besides, K<sub>V</sub> channel blocker 4-AP, K<sub>ATP</sub> channel blocker glibenclamide, and BK<sub>Ca</sub> channel blockers TEA and iberiotoxin incubations significantly inhibited the rose oil-induced relaxation responses (p < 0.05). However, incubation of tissues with DMSO, glibenclamide solvent, for 10 min did not cause a significant change in the relaxation responses to rose oil (p > 0.05). CONCLUSIONS: In conclusion, the first physiological findings were obtained regarding the functional relaxant effects of rose essential oil in rat trachea. The findings showed that rose oil induces bronchorelaxation in a concentration-dependent manner. Besides, this study is the first to report that rose oil-mediated bronchodilation responses are associated with the activity of K<sub>V</sub>, K<sub>ATP</sub>, and BK<sub>Ca</sub> channels. These results suggest that rose oil might be a useful agent in the treatment of abnormal bronchoconstriction-related diseases such as asthma and chronic obstructive pulmonary disease.

Irisin relaxes rat thoracic aorta through inhibiting signaling pathways implicating protein kinase C.

BACKGROUND: Irisin, a newly identified exercise-derived myokine, has been found involved in a peripheral vasodilator effect. However, little is known regarding the potential vascular activity of irisin, and the mechanisms underlying its effects on vascular smooth muscle have not been fully elucidated. This study was aimed to investigate the effects of irisin on vascular smooth muscle contractility in rat thoracic aorta, and the hypothesis that protein kinase C (PKC) may have a role in these effects. METHODS: Isometric contraction-relaxation responses of thoracic aorta rings were measured with an isolated organ bath model. The steady contraction was induced with 10 µM phenylephrine (PHE), and then the concentration-dependent responses of irisin (0.001-1 µM) were examined. The time-matched vehicle control (double distilled water) group was also formed. To evaluate the role of PKC, endothelium-intact thoracic aorta rings were incubated with 150 nM bisindolylmaleimide I (BIM I) for 20 min before the addition of 10 µM PHE and irisin. Also, a vehicle control group was formed for dimethyl sulfoxide (DMSO). RESULTS: Irisin exerted the vasorelaxant effects at concentrations of 0.01, 0.1, and 1 µM compared to the control group (p < 0.001). Besides, PKC inhibitor BIM I incubation significantly inhibited the relaxation responses induced by varying concentrations of irisin (p: 0.000 for 0.01 µM; p: 0.000 for 0.1 µM; p: 0.000 for 1 µM). However, DMSO, a solvent of BIM I, did not modulate the relaxant effects of irisin (p > 0.05). DISCUSSION: In conclusion, physiological findings were obtained regarding the functional relaxing effects of irisin in rat thoracic aorta. The findings demonstrated that irisin induces relaxation responses in endothelium-intact thoracic aorta rings in a concentration-dependent manner. Furthermore, this study is the first to report that irisin-induced relaxation responses are regulated probably via activating signaling pathways implicating PKC.

Irisin Relaxes Rat Trachea via KV Channels, KATP Channels, and BKCa Channels.

BACKGROUND: This study aimed to investigate the effects of irisin on rat tracheal smooth muscle contraction-relaxation responses and the roles of voltage-gated potassium (KV) channels, ATP-sensitive potassium (KATP) channels, and large-conductance calcium-activated potassium (BKCa) channels in these effects. METHODS: Isometric contraction and relaxation responses of tracheal segments were measured using the tissue bath method. Submaximal contractions were induced by ACh (10-5 M) or KCl (60 mM), and then concentration-response curves of irisin (10-9 to 10-6 M) were obtained. For the temporal control, a double-distilled water group was formed. ACh and irisin were added to the baths after tracheal segments were incubated with 4-AP (KV channel blocker), glibenclamide (KATP channel blocker), TEA, and iberiotoxin (BKCa channel blockers) to assess the role of K+ channels. In addition, a vehicle group was performed for the solvent dimethyl sulfoxide (DMSO). RESULTS: Irisin exhibited the relaxant effects in tracheal segments precontracted with both ACh and KCl at concentrations of 10-8-10-6 M (p<0.05). Besides, incubations of 4-AP, glibenclamide, TEA, and iberiotoxin significantly inhibited the irisin-mediated relaxation (p<0.05), whereas DMSO incubation did not modulate irisin responses (p>0.05). CONCLUSION: In conclusion, the first physiological results on the relaxant effects of irisin in rat trachea were obtained. Our findings demonstrated that irisin mediates concentration-dependent relaxation in rat tracheas. Moreover, the present study reported for the first time that irisin-induced bronchorelaxation is associated with the activity of the K+ channels.

Geraniol and ß-citronellol participate in the vasorelaxant effects of Rosa damascena Miller essential oil on the rat thoracic aorta.

AIM: This study aimed to investigate the vasoactive effects of Rosa damascena Miller essential oil and its major components, geraniol and ß-citronellol, on the rat thoracic aorta. METHODS: Isolated tissue bath model and Wistar rats were used to perform the experiments. Two-fold increasing concentrations (20-160 µg/mL) of rose oil were administered to determine its vasoactive effects. Submaximal contractions were induced by PE or KCl in both endothelium-intact and -denuded segments. Time-matched control groups were also formed. To evaluate the role of geraniol and ß-citronellol, concentrations in the range of 0.4-3.2 µg/mL and 0.8-6.4 µg/mL were applied respectively. The statistical significance level was considered as p < 0.05. RESULTS: All doses of rose oil applied led to vasorelaxation in thoracic aortas precontracted with PE. In precontracted thoracic aortas with KCl, the significant effect of rose oil persisted, albeit slightly diminished. When the endothelium was removed, the relaxant effect of rose oil was partially reduced, but still significant. Besides, although geraniol relaxed aortic segments at all concentrations (0.4 to 3.2 µg/mL), ß-citronellol caused vasorelaxation at doses of 1.6, 3.2, and 6.4 µg/mL. CONCLUSION: In conclusion, the first findings were obtained that rose oil can cause a vasorelaxant effect in a concentration-dependent manner in rat thoracic aorta. This effect substantially persisted in vascular segments without endothelium or precontracted with KCl. It was further shown for the first time that geraniol and ß-citronellol exert vasodilatory effects on the rat thoracic aorta. These results suggest that rose oil exhibits its vasorelaxant effect through geraniol and ß-citronellol.

Rosa damascena Miller essential oil relaxes rat thoracic aorta through the NO-cGMP-dependent pathway.

AIM: This study aimed to investigate the effects of Rosa damascena Mill. essential oil on the vascular activity of rat thoracic aorta and its underlying mechanisms. METHODS: Experiments were performed using the isolated tissue bath model and Wistar rats. 0.1, 1, 10, and 100 µg/mL concentrations of rose oil were administered in all groups. To determine the vasoactive effects of rose oil, submaximal contractions were conducted by applying 10-5 M PE and 45 mM KCl separately in both endothelium-intact and -denuded segments. Time-matched distilled water groups were formed for control. To evaluate the role of endothelium-derived vasodilative factors, endothelium-intact segments were incubated with nitric oxide synthase inhibitor L-NAME, soluble guanylate cyclase inhibitor ODQ, and a non-selective cyclooxygenase inhibitor INDO. The statistical significance level was considered as p < 0.05. RESULTS: 1, 10, and 100 µg/mL rose oil doses led to vasorelaxation in thoracic aortas precontracted with 10-5 M PE (p: 0.029, p: 0.000, p: 0.000, respectively). In precontracted thoracic aortas with 45 mM KCl, the significant effect of rose oil persisted, albeit slightly diminished. When the endothelium was removed, the relaxant effect of rose oil was partially reduced, but still significant (p: 0.035, p: 0.028, p: 0.000, respectively). Preincubations with L-NAME and ODQ significantly attenuated rose oil-induced relaxation of endothelium-intact aortas precontracted with 10-5 M PE. In contrast, preincubation INDO did not modulate rose oil-induced relaxation. CONCLUSION: In conclusion, it was shown for the first time that rose oil can significantly mediate vasorelaxation in both PE and KCl precontracted rat thoracic aortas. Rose oil induced vasodilation with or without endothelium in a concentration-dependent manner. It was also shown that rose oil-induced vasorelaxant effects were reduced by L-NAME or ODQ pretreatment, but not modulated by INDO. These results demonstrated that rose oil-induced endothelium-dependent vasodilation is mediated by the NO-cGMP-dependent pathway.

Potassium Channels Contributes to Apelin-induced Vasodilation in Rat Thoracic Aorta.

BACKGROUND: Apelin is a newly discovered peptide hormone and originally discovered endogenous apelin receptor ligand. OBJECTIVE: In this study, we aimed to investigate the possible roles of potassium channel subtypes in the vasorelaxant effect mechanisms of apelin. METHODS: The vascular rings obtained from the thoracic aortas of the male Wistar Albino rats were placed into the isolated tissue bath system. The resting tension was set to 2 g. After the equilibration period, the aortic rings were precontracted with 10-5 M phenylephrine (PHE) or 45 mM KCl. Pyroglutamyl-apelin-13 ([Pyr1]apelin-13), which is the dominant apelin isoform in the human cardiovascular tissues and human plasma, was applied cumulatively (10-10-10-6 M) to the aortic rings in the plateau phase. The experimental protocol was repeated in the presence of specific K+ channel subtype blockers to determine the role of K+ channels in the vasorelaxant effect mechanisms of apelin. RESULTS: [Pyr1]apelin-13 induced a concentration-dependent vasorelaxation (p < 0.001). The maximum relaxation level was approximately 52%, according to PHE-induced contraction. Tetraethylammonium, iberiotoxin, 4-Aminopyridine, glyburide, anandamide, and BaCl2 statistically significantly decreased the vasorelaxant effect level of [Pyr1]apelin-13 (p < 0.001). However, apamin didn't statistically significantly change the vasorelaxant effect level of [Pyr1]apelin-13. CONCLUSION: In conclusion, our findings suggest that BKCa, IKCa, Kv, KATP, Kir, and K2P channels are involved in the vasorelaxant effect mechanisms of apelin in the rat thoracic aorta.

Vascular Functional Effect Mechanisms of Elabela in Rat Thoracic Aorta.

BACKGROUND: Elabela is a recently discovered peptide hormone. The present study aims to investigate the vasorelaxant effect mechanisms of elabela in the rat thoracic aorta. METHODS: The vascular rings obtained from the thoracic aortas of the male Wistar albino rats were placed in the isolated tissue bath system. Resting tension was set to 1 gram. After the equilibration period, the vessel rings were contracted with phenylephrine or potassium chloride. Once a stable contraction was achieved, elabela-32 was applied cumulatively (10-9-10-6 molar) to the vascular rings. The experimental protocol was repeated in the presence of specific signaling pathway inhibitors or potassium channel blockers to determine the effect mechanisms of elabela. RESULTS: Elabela showed a significant vasorelaxant effect in a concentration-dependent manner (P < 0.001). The vasorelaxant effect level of elabela was significantly reduced by the apelin receptor antagonist F13A, cyclooxygenase inhibitor indomethacin, adenosine monophosphate-activated protein kinase inhibitor dorsomorphin, protein kinase C inhibitor bisindolmaleimide, large-conductance calcium-activated potassium channel blocker iberiotoxin, and intermediate-conductance calcium-activated potassium channel blocker TRAM-34 (P < 0.001). However, the vasorelaxant effect level of elabela was not significantly affected by the endothelial nitric oxide synthase inhibitor nitro-L-arginine methyl ester and mitogen-activated protein kinase inhibitor U0126. CONCLUSIONS: Elabela exhibits a prominent vasodilator effect in rat thoracic aorta. Apelin receptor, prostanoids, adenosine monophosphate-activated protein kinase, protein kinase C, and calcium-activated potassium channels are involved in the vasorelaxant effect mechanisms of elabela.

Irisin relaxes rat thoracic aorta: MEK1/2 signaling pathway, KV channels, SKCa channels, and BKCa channels are involved in irisin-induced vasodilation.

This study investigated the effects of irisin on vascular smooth muscle contractility in rat thoracic aorta, and the hypothesis that mitogen-activated protein kinase kinase (MEK1/2) signaling pathway, voltage-gated potassium (KV) channels, small-conductance calcium-activated potassium (SKCa) channels, and large-conductance calcium-activated potassium (BKCa) channels may have roles in these effects. Isometric contraction-relaxation responses of isolated thoracic aorta rings were measured with an organ bath model. The steady contraction was induced with 10-5 M phenylephrine (PHE), and then the concentration-dependent responses of irisin (10-9-10-6 M) were examined in endothelium-intact and -denuded rat thoracic aortas. Also, the effects of irisin incubations on PHE-mediated contraction and acetylcholine (ACh) - mediated relaxation were studied. Irisin exerted the vasorelaxant effects in both endothelium-intact and -denuded aortic rings at concentrations of 10-8, 10-7, and 10-6 M compared with the control groups (p < 0.001). Besides, pre-incubation of aortic rings with irisin (10 nM, 100 nM, or 1 µM for 30 min) augmented ACh-mediated (10-9-10-5) vasodilation in PHE-precontracted thoracic aorta segments but did not modulate PHE-mediated (10-9-10-5) contraction. In addition, MEK1/2 inhibitor U0126, KV channel blocker XE-991, SKCa channel blocker apamin, and BKCa channel blocker tetraethylammonium (TEA) incubations significantly inhibited the irisin-induced relaxation responses. In conclusion, the first physiological findings were obtained regarding the functional relaxing effects of irisin in rat thoracic aorta. The findings demonstrated that irisin induces relaxation responses in endothelium-intact and (or) endothelium-denuded aortic rings in a concentration-dependent manner. Furthermore, this study is the first to report that irisin-induced relaxation responses are related to the activity of the MEK1/2 pathway, KV channels, and calcium-activated K+ (SKCa and BKCa) channels.

Physiological role of K+ channels in irisin-induced vasodilation in rat thoracic aorta.

Irisin, an exercise-induced myokine, has been shown to have a peripheral vasodilator effect. However, little is known about the mechanisms underlying its effects. In this study, it was aimed to investigate the vasoactive effects of irisin on rat thoracic aorta, and the hypothesis that voltage-gated potassium (KV) channels, ATP-sensitive potassium (KATP) channels, small-conductance calcium-activated potassium (SKCa) channels, large-conductance calcium-activated potassium (BKCa) channels, intermediate-conductance calcium-activated potassium (IKCa) channels, inward rectifier potassium (Kir) channels, and two-pore domain potassium (K2P) channels may have roles in these effects. Isometric contraction-relaxation responses of isolated thoracic aorta rings were measured with an organ bath model. The steady contraction was induced with both 10-5 M phenylephrine and 45 mM KCl, and then the concentration-dependent responses of irisin (10-9-10-6 M) were examined. Irisin exerted the vasorelaxant effects in both endothelium-intact and -denuded aortic rings at concentrations of 10-8, 10-7, and 10-6 M (p < 0.001). Besides, KV channel blocker 4-aminopyridine, KATP channel blocker glibenclamide, SKCa channel blocker apamin, BKCa channel blockers tetraethylammonium and iberiotoxin, IKCa channel blocker TRAM-34, and Kir channel blocker barium chloride incubations significantly inhibited the irisin-induced relaxation responses. However, incubation of K2P TASK-1 channel blocker anandamide did not cause a significant decrease in the relaxation responses of irisin. In conclusion, the first physiological findings were obtained regarding the functional relaxing effects of irisin in rat thoracic aorta. Furthermore, this study is the first to report that irisin-induced relaxation responses are associated with the activity of KV, KATP, SKCa, BKCa, IKCa, and Kir channels.

Medical Evaluation of the Antimicrobial Activity of Rose Oil on Some Standard Bacteria Strains and Clinical Isolates.

Introduction: Considerable interest has developed concerning the alternative utilization of aromatic plants rich in essential oils as antibacterial agents in the medical arena. In this study, we investigated the antimicrobial activity for solutions of different concentrations of rose oil on test microorganisms known to potentially have an adverse affect on human health and the environment. Methods: Research was carried out by the microdilution method. The test microorganisms were standard strains and clinical isolates (CIs) of Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Acinetobacter baumannii ATCC 17978, Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 25923 and Streptococcus pneumonia ATCC 49619. Results: E coli was inhibited by a minimal concentration of 125 µl/ml rose oil dilution of both the standard strain and CI, B subtilis by a minimal concentration of 15.62 µl/ml and 31.25 µl/ml rose oil dilutions of the standard strain and CI, respectively, and S aureus by a minimal concentration of 31.25 µl/ml and 125 µl/ml of rose oil dilutions standard strain and CI, respectively. Thus, it was determined that rose oil could exhibit antimicrobial activity in both Gram-positive and Gram-negative bacteria. Discussion/Conclusions: Different percentages of diluted solutions of rose oil might be used as a preventive and therapeutic treatment for infections caused by E coli, B subtilis, and S aureus, provided that this is supported by evidence from clinical trials. Consequently, natural antimicrobial rose oil may have beneficial effects on human and environmental health.

[Pyr1]apelin-13 relaxes the rat thoracic aorta via APJ, NO, AMPK, and potassium channels.

In this study, the effect and effect mechanisms of [Pyr1]apelin-13, the dominant apelin isoform in the human cardiovascular tissues and human plasma, on vascular contractility were investigated. The vascular rings obtained from the thoracic aortas of the male Wistar Albino rats were placed in the isolated tissue bath system. After the equilibration period, [Pyr1]apelin-13 (10-9 to 10-6 M) was applied cumulatively to the aortic rings pre-contracted with phenylephrine in the plateau phase. The protocol was repeated in the presence of specific signaling pathway inhibitors (F13A, L-NAME, dorsomorphin, TEA, U0126, or indomethacin) to determine the effect mechanisms of [Pyr1]apelin-13. [Pyr1]apelin-13 induced a dose-dependent relaxation in the pre-contracted aortic rings. APJ, eNOS, AMPK, and potassium channel inhibition statistically significantly decreased the vasodilator effect of [Pyr1]apelin-13. MAPK and COX inhibition didn't statistically significantly changed the vasodilator effect of [Pyr1]apelin-13. In conclusion, [Pyr1]apelin-13 relaxes the rat thoracic aorta via APJ, NO, AMPK, and potassium channels.

Morning blood pressure surge in early autosomal dominant polycystic kidney disease and its relation with left ventricular hypertrophy.

INTRODUCTION: The activation of the sympathetic nervous system, which usually leads to a swift surge in blood pressure in the morning hours (MBPS) may be the cause of left ventricular hypertrophy (LVH) and endothelial dysfunction (ED) in early autosomal dominant polycystic kidney disease (ADPKD) patients. We studied the association between MBPS and LVH in ADPKD patients with preserved renal functions. METHODS: Patients with ADPKD with preserved renal functions were enrolled. Prewaking MBPS was calculated using ambulatory blood pressure monitoring. The patients were categorized as MBPS (≥median) and non-MBPS (