Efecto del 4-Clorofenol sobre el músculo liso vascular de aorta abdominal de ratas Wistar / Effect of 4-Chlorophenol on the vascular smooth muscle of the abdominal aorta of Wistar rats

Introducción: Uno de los derivados de los clorofenoles más utilizado en Estomatología, lo constituye el p-clorofenol (4-clorofenol), empleado como agente antibacteriano en la desinfección del conducto radicular durante el tratamiento pulporradicular. Son escasos los reportes científicos sobre sus efectos en la musculatura lisa vascular arterial y la regulación del flujo sanguíneo local. Objetivo: Determinar el efecto del 4-clorofenol sobre el músculo liso vascular de aorta abdominal de ratas Wistar. Material y Métodos: Se realizó una investigación experimental preclínica, utilizando 30 anillos de aorta abdominal (porción superior) obtenidos de ratas Wistar adultas. Las preparaciones de unos 5 mm se colocaron en baño de órganos, registrándose la tensión desarrollada por el músculo liso vascular tras la adición de 4-clorofenol en diferentes concentraciones y durante diferentes intervalos de tiempo. Resultados: El 4-clorofenol, tras la preactivación del musculo liso vascular de anillos de aorta abdominal, indujo relajación del vaso, la que se incrementó durante todo el tiempo de estudio y al aumento de la concentración del medicamento. Existieron diferencias significativas entre los valores de tensión promedios registrados en los diferentes intervalos de tiempo con los de la tensión base inicial. Conclusiones: El p-clorofenol indujo in vitro, relajación del músculo liso vascular de aorta abdominal de ratas Wistar(AU)

Introduction: In Dentistry, p-chlorophenol (4-chlorophenol) is one of the most widely used derivatives of chlorophenols. It is used as an antibacterial agent in root canal disinfection during pulp-radicular treatment. There are few scientific reports on its effects on vascular smooth musculature and the regulation of local blood flow. Objective: To determine the effect of 4-chlorophenol on vascular smooth muscle of abdominal aorta from Wistar rats. Material and Methods: A preclinical experimental research was carried out using 30 abdominal aortic rings (upper portion) obtained from adult Wistar rats. The preparations of about 5 mm were placed in an organ bath, recording the tension developed by the vascular smooth muscle after the addition of 4-chlorophenol at different concentrations and during different time intervals. Results: The results demonstrate that 4-Chlorophenol induced vasorelaxation after the preactivation of the vascular smooth muscle of the abdominal aortic rings, which increased during the entire study time and with increased drug concentration. There were significant differences among average tension values registered at different intervals of time in relation to the initial base tension. Conclusions: It is concluded that in vitro, p-chlorophenol induced relaxation of abdominal aorta vascular smooth muscle in Wistar rats(AU)

α-Isocubebene modulates vascular tone by inhibiting myosin light chain phosphorylation in murine thoracic aorta

α-Iso-cubebene (ICB) is a dibenzocyclooctadiene lignin contained in Schisandra chinensis (SC), a well-known medicinal herb that ameliorates cardiovascular symptoms, but the mechanism responsible for this activity has not been determined. To determine the role played by ICB on the regulation of vascular tone, we investigated the inhibitory effects of ICB on vascular contractile responses by adrenergic α-receptor agonists. In addition, we investigated the role on myosin light chain (MLC) phosphorylation and cytosolic calcium concentration in vascular smooth muscle cells (VSMC). In aortic rings isolated from C57BL/6J mice, ICB significantly attenuated the contraction induced by phenylephrine (PE) and norepinephrine (NE), whereas ICB had no effects on KCl (60 mM)-induced contraction. In vasculatures precontracted with PE, ICB caused marked relaxation of aortic rings with or without endothelium, suggesting a direct effect on VSMC. In cultured rat VSMC, PE or NE increased MLC phosphorylation and increased cytosolic calcium levels. Both of these effects were significantly suppressed by ICB. In conclusion, our results showed that ICB regulated vascular tone by inhibiting MLC phosphorylation and calcium flux into VSMC, and suggest that ICB has anti-hypertensive properties and therapeutic potential for cardiovascular disorders related to vascular hypertension.

Time course of the hemodynamic responses to aortic depressor nerve stimulation in conscious spontaneously hypertensive rats

The time to reach the maximum response of arterial pressure, heart rate and vascular resistance (hindquarter and mesenteric) was measured in conscious male spontaneously hypertensive (SHR) and normotensive control rats (NCR; Wistar; 18-22 weeks) subjected to electrical stimulation of the aortic depressor nerve (ADN) under thiopental anesthesia. The parameters of stimulation were 1 mA intensity and 2 ms pulse length applied for 5 s, using frequencies of 10, 30, and 90 Hz. The time to reach the hemodynamic responses at different frequencies of ADN stimulation was similar for SHR (N = 15) and NCR (N = 14); hypotension = NCR (4194 ± 336 to 3695 ± 463 ms) vs SHR (3475 ± 354 to 4494 ± 300 ms); bradycardia = NCR (1618 ± 152 to 1358 ± 185 ms) vs SHR (1911 ± 323 to 1852 ± 431 ms), and the fall in hindquarter vascular resistance = NCR (6054 ± 486 to 6550 ± 847 ms) vs SHR (4849 ± 918 to 4926 ± 646 ms); mesenteric = NCR (5574 ± 790 to 5752 ± 539 ms) vs SHR (5638 ± 648 to 6777 ± 624 ms). In addition, ADN stimulation produced baroreflex responses characterized by a faster cardiac effect followed by a vascular effect, which together contributed to the decrease in arterial pressure. Therefore, the results indicate that there is no alteration in the conduction of the electrical impulse after the site of baroreceptor mechanical transduction in the baroreflex pathway (central and/or efferent) in conscious SHR compared to NCR.

Effect of pH Change on Vascular Smooth Muscle Contractility in Rat Superior Mesenteric Artery and Its Branches / 대한흉부외과학회지

BACKGROUND: Extracellular and intracellular pH (pHo and pHi), which can be changed in various pathological conditions such as hypoxia, affects vascular contractility. To elucidate the mechanism to alter vascular contractility by pH, the effects of pH on reactivity to vasocontracting agents, intracellular Ca2+ influx, and Ca2+ sensitivity in vascular smooth muscle were examined. MATERIAL AND METHOD: Isometric contractions in rat superior mesenteric arteries (SMA) were observed. Intracellular Ca2+ concentration ([Ca2+]i) was recorded by microfluorometer using Fura-2/acetoxylmethyl ester in muscle cells. pHo was increased from 7.4 to 7.8 or decreased to 6.9 or 6.4. pHi was decreased by applying NH4+ or propionic acid or modulated by changing pHo after increasing membrane permeability using beta-escin. RESULT: Decreases in pHo from 7.4 to 6.9 or 6.4 shifted concentration-response curve by norepinephrine (NE) or serotonin (SE) to the right and significantly increased half maximal effective concentration (EC50) to NE or SE. Increase in pHo from 7.4 to 7.8 shifted concentration-response curve by norepinephrine (NE) or serotonin (SE) to the left and significantly reduced EC50 to NE or SE. NE increased [Ca2+]i in cultured smooth muscle cells from SMA and the increased [Ca2+]i was reduced by decreases in pHo. NE-induced contraction was inhibited by NH4+, whereas the resting tension was increased by NH4+ or propionic acid. When the cell membrane of SMA was permeabilized using beta-escin, SMA was contracted by increasing extracellular Ca2+ concentration from 0 to 10micrometer and the magnitude of contraction was decreased by a decrease in pHo and vice versa. CONCLUSION: From these results, it can be concluded that a decrease in pHo might inhibit vascular contraction by reducing the reactivity of vascular smooth muscle to vasoactive agents, Ca2+ influx and the sensitivity of vascular smooth muscle to Ca2+.

The Change of Vascular Reactivity in Rat Thoracic Aorta 3 Days afterAcute Myocardial Infarction / 대한흉부외과학회지

BACKGROUND: The up-regulation of the nitric oxide (NO)-cGMP pathway might be involved in the change of vascular reactivity in rats 3 days after they suffer acute myocardial infarction. However, the underlying mechanism for this has not been clarified. MATERIAL AND METHOD: Acute myocardial infarction (AMI) was induced by occluding the left anterior descending coronary artery (LAD) for 30 min (Group AMI), whereas the sham-operated control rats were treated similarly without LAD occlusion (Group SHAM). The concentration-response relationships for phenylephrine (PE), KCl, acetylcholine (Ach) and sodium nitroprusside (SNP) were determined in the endothelium intact E(+) and endothelium denuded E(-) thoracic aortic rings from the rats 3 days after AMI or a SHAM operation. The concentration-response relationships of PE in the E(+) rings from the AMI rats were compared with those relationships in the rings pretreated with nitric oxide synthase (NOS) inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) or the cyclooxygenase inhibitor indomethacin. The plasma nitrite/nitrate concentrations were checked via a Griess reaction. The cyclic GMP content in the thoracic aortic rings was measured by radioimmunoassay and the endothelial nitric oxide synthase (eNOS) mRNA expression was assessed by real time PCR. RESULT: The mean infarct size (%) in the rats with AMI was 21.3+/-0.62%. The heart rate and the systolic and diastolic blood pressure were not significantly changed in the AMI rats. The sensitivity of the contractile response to PE and KCl was significantly decreased in both the E(+) and E(-) aortic rings of the AMI group (p<0.05). L-NAME completely reversed these contractile responses whereas indomethacin did not (p<0.05). Moreover, the sensitivity of the relaxation response to Ach was also significantly decreased in the AMI group (p<0.05). The plasma nitrite and nitrate content (p<0.05), the basal cGMP content (p<0.05) and the eNOS mRNA expression (p=0.056) in the AMI rats were increased as compared with the SHAM group. CONCLUSION: Our findings indicate that the increased eNOS activity and the up-regulation of the NO-cGMP pathway can be attributed to the decreased contractile or relaxation response in the rat thoracic aorta 3 days after AMI.

Effects of pH on Vascular Tone in Rabbit Basilar Arteries

Effects of pH on vascular tone and L-type Ca2+ channels were investigated using Mulvany myograph and voltage-clamp technique in rabbit basilar arteries. In rabbitbasilar arteries, high K+ produced tonic contractions by 11+/-0.6 mN (mean+/-S.E., n=19). When extracellular pH (pHo) was changed from control 7.4 to 7.9 ([alkalosis]o), K+-induced contraction was increased to 128+/-2.1% of the control (n=13). However, K+-induced contraction was decreased to 73+/-1.3% of the control at pHo 6.8 ([acidosis]o, n=4). Histamine (10 micrometer) also produced tonic contraction by 11+/-0.6 mN (n=17), which was blocked by post-application of nicardipine (1 micrometer). [alkalosis]o and [acidosis]o increased or decreased histamine-induced contraction to 134+/-5.7% and 27+/-7.6% of the control (n=4, 6). Since high K+- and histamine-induced tonic contractions were affected by nicardipine and pHo, the effect of pHo on voltage-dependent L-type Ca2+ channel (VDCCL) was studied. VDCCL was modulated by pHo: the peak value of Ca2+ channel current (IBa) at a holding of 0 mV decreased in [acidosis]o by 41+/-8.8%, whereas that increased in [alkalosis]o by 35+/-2.1% (n=3). These results suggested that the external pH regulates vascular tone partly via the modulation of VDCC in rabbit basilar arteries.

Altered Resting Nitric Oxide Vasodilator Tone in Two-Kidney, One Clip Rats / 대한신장학회잡지

Endogenous nitric oxide(NO) plays an important role in the regulation of blood pressure. It has been known that the evoked NO-dependent dilator system may be impaired in various hypertensive models. The effects of NG-nitro-L-arginine(L-NNA), lipopolysaccharide(LPS) and tempol on mean arterial pressure(MAP) and the effects of L-NNA on isolated aorta tone were studied in order to elucidate potential alterations in resting vasodilator tone of NO in two-kidney, one clip(2K1C) hypertension. Plasma nitrite/nitrate levels were measured by colorimetric assay, and the expression of endothelial and inducible NO synthases(eNOS, iNOS) was determined by Western blot analysis. L-NNA caused an increase of MAP, while LPS produced a hypotensive effect in both 2K1C and control rats. The magnitude of the pressor or depressor response to L-NNA and LPS was comparable in the two groups. Tempol induced a sustained decrease in MAP in 2K1C rats, while it had no effects on MAP in control rats. Plasma concentrations of NO metabolites were significantly increased following the LPS-treatment in both 2K1C and control rats, while they were not affected by tempol-treatment. In endothelium-intact aortic rings precontracted with 25 mM KCl, L-NNA caused a dose-dependent contraction. The magnitude of the maximal contraction was attenuated in 2K1C rats as compared with control. An inhibition of contractile responses to L-NNA in the hypertensive group was also shown in rubbed rings, although the magnitude of contractions was markedly reduced. The vascular expression of both eNOS and iNOS was significantly decreased in 2K1C rats as compared with control. These results indicate that 2K1C hypertension is associated with a reduced basal vasodilator tone of NO and a decrease in the vascular expression of NOS isozymes.

Estrogen affects vascular tone differently according to vasoactive substances in ovariectomized Sprague-Dawley rat

The favorable effects of estrogen on cardiovascular diseases can be explained by several mechanisms such as changes in serum lipid profiles and thrombogenecity. Estrogen also affects the vascular tone, but there has been no report in which the effect of estrogen was tested comprehensively for several vasoactive substances, especially after long-term administration. Two weeks after bilateral ovariectomy in 8-week old female Sprague-Dawley rats, placebo or 17 beta-estradiol (E2) pellets (0.5 mg; released over 3 weeks) were implanted subcutaneously. Two weeks after pellet implantation, organ chamber experiments were performed using aortae. Compared with control, E2-treated vessels showed impaired endothelium-dependent relaxation to acetylcholine. E2 enhanced the contraction to norepinephrine and U46619 and had no effect on endothelin-1-induced contraction. In contrast, the contraction to angiotensin (AT)-II was inhibited by E2. Northern blot analysis for AT1 receptor expression using cultured aortic smooth muscle cells showed no difference between control and E2-treated cells, suggesting that AT1 receptor downregulation is not the likely mechanism. These results suggest that E2 affects the vascular tone variably according to vasoactive substances.

Effects of Acid-Base Balance on the Isolated Rabbit Vascular Tone / 대한마취과학회지

The effects of acidosis and alkalosis on vascular smooth muscle contractions were studied. Ring segments(3-4 mm in length) of rabbit abdominal aorta and pulmonary artery were mounted in the tissue bath(for respiratory study) and superfusion device(for metabolic study) for isometric tension recording. Respiratory acidosis and alkalosis were obtained by increasing and lowering the PCO2(80 and 15 mmHg, respectively). Metabolic acidosis and alkalosis were obtained by lowering and increasing the HCO3 concentration(12 and 50 mEq/l, respectively). After precontraction with norepinephrine(10-7 M), Vessels were exposed to acidosis and alkalosis for 30 minutes. The study was done with and without endothelium. The mechanism of vasorelaxation and vasoconstriction were confirmed with Ca2+ activated K+ channel blocker and Ca2+ free Krebs solution. The results were as follows: 1) Respiratory and metabolic acidosis induced significant vasorelaxation in both group of abdominal aorta and pulmonary artery(p<0.05). In endothelium intact group, vasorelaxation was greater than endothelium removed group. especially in respiratory acidosis was statistically significant(p<0.05). 2) Respiratory and metabolic alkalosis induced significant vasoconstriction in both group of abdominal aorta and pulmonary artery(p<0.05). In endothelium intact group, vasoconstriction was lesser than endothelium removed group, but was not statistically significant. 3) Acidosis induced vasorelaxation was blocked by tetraethylammonium(TEA). 4) Alkalosis induced vasoconstriction was blocked by Ca2+ free Krebs solution. These results suggested that: 1) Acidosis induced vasorelaxation. 2) alkalosis induced vasoconstriction 3) Vasorelaxation during acidosis was induced by K+ efflux through the Ca2+ activated K' channel. 4) Vasoconstriction during alkalosis was induced by Ca2+ influx.