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PubMed2003

Inhaled nitric oxide modifies left ventricular diastolic stress in the presence of vasoactive agents in heart failure.

Nitric oxide (NO) inhalation therapy has been widely used in several diseases with pulmonary hypertension. However, application of NO inhalation therapy remains controversial in heart failure. Cardiovascular effects of inhaled NO (iNO) were evaluated in dogs before and after induction of heart failure with and without infusion of vasoactive agents. iNO did not affect the baseline left ventricular (LV) function or the response to isoproterenol in control conditions or heart failure induced by procainamide. Pulmonary vascular resistance was significantly decreased by iNO in heart failure with infusion of vasoactive agents. Unexpectedly, LV end-diastolic pressure was significantly elevated by iNO in heart failure in the presence of infusion of vasoactive agents independent of their types; either the vasodilating agents of acetylcholine and nitroglycerin or the vasoconstricting agents of norepinephrine and angiotensin-II. The end-diastolic LV dimension and wall stress were also significantly increased by iNO, however, those at end systole were not affected. These results suggested that NO inhalation therapy reduced pulmonary vascular resistance, whereas in the presence of additional stress of vasoactive agents, it increased LV preload and end-diastolic wall stress in heart failure.

Acetylcholine↗
PubMed2000

Vasoactive agents modulate migration of monocytes across glomerular endothelial cells.

BACKGROUND: Macrophages seem to play an important role in the development of glomerulosclerosis. In both human and experimental animal models of focal glomerulosclerosis (FSGS), infiltration of macrophages in the mesangium has been considered key in the development of FSGS. METHODS: In the present study, we evaluated the effect of vasoactive agents on the migration of monocytes across a filter in a modified Boyden chamber as well as across a cultured glomerular endothelial cell layer (in vitro model of glomerular mesangium). Both light as well as scanning electron microscopic studies were performed. We evaluated the effect of vasoactive agents including histamine, prostaglandin (PG) E2, angiotensin II, endothelin-1, platelet-activating factor, and interleukin-1 (IL) on the migration of monocytes/macrophages across an endothelial cell layer as well as a gelatin-coated filter. In addition, we evaluated the effect of cyclic adenosine 3',5' cyclic monophosphate (cAMP) and PGE2 on vasoactive-induced migration of monocytes. RESULTS: Histamine increased (P < 0.003) the migration of monocytes across the filter. This effect of histamine was dose-dependent. Histamine at concentrations of 10(-8) to 10(-5) mol/L induced optimal migration across the filter (control, 16.6 +/- 1.1 vs histamine, 10(-8) mol/L, 40.9 +/- 0.9 monocytes/high power field). Cimetidine, an H2 receptor blocker, attenuated (P < 0.001) the effect of histamine on the migration of monocytes. PGE2 inhibited the migration of monocytes in a dose-dependent manner. Histamine increased (P < 0.001) the passage of monocytes across the glomerular endothelial cell layer (control, 1012 +/- 37 vs 1711 +/- 163 cpm/well). Histamine also increased the migration of murine macrophages across the glomerular endothelial cell layer. PGE2 inhibited the migration of monocytes across the endothelial cell layer under basal as well as histamine-stimulated states. Dibutyryl cyclic (DBc) AMP also attenuated the migration of monocytes under basal as well as histamine-stimulated states. Both PGE2 and DBcAMP also attenuated the IL-1 beta-stimulated migration of monocytes. Angiotensin II, endothelin-1, and platelet-activating factor did not modulate the migration of monocytes. CONCLUSIONS: Vasoactive agents directly modulate the transmigration of monocytes. The present in vitro study provides a basis for a hypothesis that vasoactive agents may also be modulating the migration of monocytes across the glomerular endothelial cell layer (into the mesangium).

Animals↗
PubMed2025

Vasoactive Agent Therapy in Septic Shock: From Monotherapy Battles to Tailored Hemodynamic Optimization.

Hemodynamic stabilization and preservation of organ perfusion are central elements in the management of septic shock. This is achieved by fluid resuscitation and by administration of vasoactive agents to secure a time window for definitive cause-directed therapy. Guided by the Surviving Sepsis Campaign, the optimization of vasoactive agent strategies, namely protective hemodynamic management, has become a central focus. Tracing key research over the past 25 years reveals a paradigm shift in vasopressor therapy, from empiricism to goal-directed strategy. This evolution has deepened our understanding of the benefit-risk profile of vasoactive agents and fostered a new conceptual framework regarding organ perfusion and protection. Under this framework, management strategies have advanced from the mere pursuit of hemodynamic parameters to care bundles that integrate the monitoring of organ perfusion, microcirculation, and oxygen metabolism. These advances have optimized agent selection, established safe dosing ranges, and ultimately promoted the widespread adoption of combined and multimodal therapy concepts. This review delineates this transformative journey, synthesizing evidence on the reappraisal of traditional agents and exploring "de-catecholaminization" strategies, thereby aiming to broaden the therapeutic landscape. The integration of artificial intelligence and genomic medicine is expected to further advance personalized management strategies for septic shock.

Humans↗
PubMed2002

Effects of indomethacin on responses of regional kidney perfusion to vasoactive agents in rabbits.

1. To determine whether differential release of products of arachidonic acid metabolism, via the cyclo-oxygenase pathway, underlies the diversity of responses of regional kidney perfusion to vasoactive agents, we tested the effects of intravenous indomethacin on responses to renal arterial bolus doses of vasoactive agents in pentobarbitone-anaesthetized rabbits. 2. Total renal blood flow (RBF) and regional kidney perfusion were determined by transit time ultrasound flowmetry and laser-Doppler flowmetry, respectively. 3. Responses of regional kidney blood flow to vasoactive agents were diverse: noradrenaline reduced cortical but not medullary perfusion, [Phe 2,Ile 3,Orn 8]-vasopressin reduced medullary perfusion more than cortical perfusion, endothelin-1 and angiotensin II increased medullary perfusion in the face of reduced cortical perfusion, while acetylcholine, bradykinin and the nitric oxide donor methylamine hexamethylene methylamine (MAHMA) NONOate all increased both cortical and medullary perfusion. 4. Indomethacin administration was followed by reductions in total RBF (17 +/- 6%), cortical perfusion (13 +/- 5%) and medullary perfusion (40 +/- 8%). Angiotensin II- and endothelin-1-induced increases in medullary perfusion were abolished by indomethacin, but indomethacin had no significant effects on responses of regional kidney perfusion to acetylcholine, bradykinin, MAHMA NONOate, noradrenaline and [Phe 2,Ile 3,Orn 8]-vasopressin. 5. Our results suggest that vasodilator cyclo-oxygenase products contribute to the maintenance of resting renal vascular tone, particularly in vascular elements controlling medullary perfusion. Cyclo-oxygenase products also appear to mediate endothelin-1- and angiotensin II-induced increases in medullary perfusion. However, regionally specific engagement of cyclo-oxygenase-dependent arachidonic acid metabolism does not appear to contribute to the differential effects of noradrenaline and [Phe 2,Ile 3,Orn 8]-vasopressin on cortical and medullary perfusion.

Animals↗
PubMed1994

Insulin attenuates intracellular calcium responses and cell contraction caused by vasoactive agents.

In the present study, we examined the effects of insulin and insulin-like growth factor I (IGF-I) on cultured rat mesangial cell responses to vasoactive agents. Intracellular calcium concentration ([Ca2+]i) was measured with the Fura-2 method in suspended mesangial cells. Pretreatment of mesangial cells with insulin (from 0.05 to 5 micrograms/ml) attenuated Ca2+ transients by platelet activating factor (PAF) in a dose dependent and a time dependent manner. Insulin also attenuated sustained elevation of [Ca2+]i elicited by PAF. Basal [Ca2+]i was not affected by insulin pretreatment. Since the effective dose of insulin (0.5 microgram/ml or higher) is much higher than the physiological concentration, the effects of insulin may be via IGF-I receptor. Indeed, IGF-I (50 ng/ml) similarly attenuated [Ca2+]i responses to PAF. Moreover, insulin pretreatment attenuated [Ca2+]i responses evoked by angiotensin II (Ang II) and endothelin-1. In addition, the pretreatment with insulin or IGF-I inhibited mesangial cell contraction in response to Ang II. The suppression of [Ca2+]i responses to vasoactive agents by insulin was abolished when extracellular Ca2+ was removed. These data suggest that insulin, probably via IGF-I receptor, attenuates [Ca2+]i responses and cell contraction of mesangial cells induced by vasoactive agents. It is likely that the change in Ca2+ influx from outside to inside the cell underlie the effect of insulin. The modification of mesangial cell function through IGF-I receptor may play a role in the regulation of glomerular hemodynamics.

Angiotensin II↗
PubMed1989

Penile response to intracavernosal vasoactive intestinal polypeptide alone and in combination with other vasoactive agents.

Intracavernosally injected vasoactive intestinal polypeptide (VIP) (2 micrograms and 4 micrograms) resulted in penile tumescence even in men with predominantly organic impotence. Papaverine and phentolamine were successful in inducing erections in all subjects studied but the addition of VIP to this combination improved the erectile response further. A combination of papaverine and VIP produced penile rigidity similar to that with papaverine and phentolamine. While intracavernosal VIP alone produced disappointing penile responses, its combination with papaverine potentiated the response to this drug, probably by increasing venous outflow resistance.

Adult↗
PubMed1987

Changes in vascular responsiveness to vasoactive agents in the hindlimb of DOCA-salt hypertensive rats.

The responsiveness to vasoactive agents in the perfused hindlimb of DOCA-salt hypertensive rats was examined and compared with that of normotensive rats. The vasoconstrictor responses in the femoral vascular bed to norepinephrine and serotonin were markedly potentiated in DOCA-salt hypertensive rats as compared with those in normotensive rats, and no change was found in the responses to angiotensin II. On the other hand, the vasodilatory response in DOCA-salt hypertensive rats to isoproterenol was attenuated without any marked changes in responsiveness to acetylcholine, nitroprusside and papaverine. These results suggested that the reduced vasodilator responses as well as the increased vasoconstrictor responses occur to some specific vasoactive agents in DOCA-salt hypertensive rats.

Angiotensin II↗
PubMedDate not supplied

Facilitated diffusion by iontophoresis of vasoactive agents to the rat incisor pulp.

The use of iontophoresis for facilitated diffusion of vasoactive agents into the dental pulp was investigated in lower incisor teeth of anaesthetized rats. Acetylcholine, carbachol and noradrenaline were iontophoresed with anodal and sodium nitroprusside with cathodal direct current through a superficial dentin exposure. Pulpal blood flow was measured with laser Doppler flowmetry. Current intensities below 100 microA of both polarities, using sodium chloride as a medium, caused no or minor afferent nerve-induced vasodilation, but excited sympathetic fibres of the pulp in a current-dependent manner. The current threshold for facilitated diffusion of acetylcholine was about 20 microA. The vascular responses to the cholinergic and noradrenergic drugs appeared within a minute after the onset of current and they were abolished by systemic administration of atropine and phenoxy benzamine, respectively. Iontophoresis of acetylcholine (40-100 microA for 20-120 s) caused a 3-fold increase of pulpal blood flow which was not dose-dependent; carbachol provoked a high-magnitude, long-lasting vasodilation and so did sodium nitroprusside. Noradrenaline caused a long-lasting vasoconstriction. In denervated rats iontophoresis of carbachol had effects similar to those seen in intact animals. None of the drugs used locally had any effect on systemic blood pressure. The results of this study indicate that iontophoresis can be used for delivery of vasoactive agents from an exposed dentin surface into the pulp in sufficient quantity to elicit drug-specific local vascular responses without causing systemic vascular effects.

Acetylcholine↗
PubMedDate not supplied

Effects of long-term intrarenal angiotensin II infusion on renal vascular responsiveness to vasoactive agents.

1. We tested whether chronic intrarenal angiotensin II (AngII) infusion altered renal vascular responsiveness to vasoactive agents, which would provide evidence of vascular structural changes. 2. The renal blood flow (RBF) responses to renal arterial administration of bolus doses of acetylcholine, glyceryl trinitrate, AngII and noradrenaline were measured before commencement of and 1 day after cessation of 28 days intrarenal AngII infusion (0.5 ng/kg per min) in chronically instrumented conscious dogs. 3. The RBF responses to these vasoactive agents were unaltered by chronic intrarenal AngII infusion in conscious dogs. 4. These functional studies provide no evidence for renal vascular hypertrophy in response to chronic intrarenal AngII infusion in conscious dogs.

Acetylcholine↗
PubMed1989

Effect of several vasoactive agents on guanylate cyclase activity in isolated rat brain microvessels.

We tested the ability of the following putative vasoactive agents to stimulate guanylate cyclase activity in isolated rat cerebral microvessels: angiotensin II, arginine vasopressin, atrial natriuretic peptide, bradykinin, carbachol and thrombin; at concentrations ranging between 10(-3) and 10(-9) M. The ability of cerebral microvessels to increase their cyclic GMP generation was ascertained in the presence of sodium nitroprusside. Of all the agents tested, only atrial natriuretic peptide stimulated cyclic GMP generation in isolated rat cerebral microvessels. Such stimulation was dose-dependent, reaching its maximum at 1 microM concentration. These results are consistent with the finding of atrial natriuretic peptide receptors in brain microvessels, and suggest that this peptide has an important role in modulating the function of brain capillaries, which constitute the blood-brain barrier. If receptors for the other vasoactive agents exist in brain microvessels, their action does not seem to be mediated by cyclic GMP as a second messenger.

Angiotensin II↗
PubMed1992

The response of spontaneous and transplantable murine tumors to vasoactive agents measured by 31P magnetic resonance spectroscopy.

31P magnetic resonance spectroscopy has been used to compare the effects of the vasoactive agents hydralazine and flunarizine on the oxygenation of the transplantable tumors, SCCVII/Ha and 16C, and a range of spontaneous mammary tumors arising in the breeding stock in the Genetics Division at the Radiobiology Unit. The vasodilator hydralazine, previously shown to increase the radiobiological hypoxic fraction of transplantable murine tumors, increased inorganic phosphate to total phosphate (Pi/total) in SCCVII/Ha and 16C tumors. However, only two spontaneous tumors responded to this agent (2/12). The calcium antagonist flunarizine, which sensitizes the SCCVII tumor to X rays, consistent with a reduction in hypoxic fraction, reduced Pi/total in this and the 16C tumor. Further, most spontaneous tumors tested (8/10) responded to this agent, as measured by a reduction in Pi/total. These results point to fundamental differences between transplantable and spontaneously arising tumors in mice in their response to vasoactive agents.

Animals↗
PubMed2002

Rat renal function four days after bile-duct ligation: effects of indomethacin and vasoactive agents.

The purpose of this study was to assess the effects of the cyclooxygenase inhibitor, indomethacin, and some vasoactive agents on the renal functional parameters during the early liver injury induced by four days bile duct ligation (BDL). Wistar rats with four days-BDL and control-sham operated were used. Renal function was measured in anesthetized rat treated with a single dose of indomethacin (control, 0.3, 1.0, 3.0 mg/kg b.w.; i.v.) one hour before clearance studies. Sulindac effects were also evaluated (5 mg/kg b.w., i.p). Isolated rat kidney preparations from control and BDL donor rats were used to study renal vascular response to noradrenaline, carbachol or sodium nitroprusside. The bile duct ligation promoted a diminished renal cortical plasma flow (RCPF) on the fourth day post surgery accompanied with a diminution in the glomerular filtration rate (GFR), increased filtration fraction and increased fractional excretion of water and sodium. Indomethacin 0.3 mg/kg induced an increase in GFR and RCPF, maintaining the high filtration fraction in BDL rats. The other doses did not alter these parameters as compared with bile duct ligated rats without treatment, but indomethacin 3 mg/kg caused a significant increase in filtration fraction. Indomethacin induced dose-dependent diminution in natriuresis in sham and BDL groups. Sulindac did not modify hemodynamic parameters, but induced antinatriuresis and antidiuresis in both experimental groups. Maximal vascular responses to noradrenaline measured in isolated rat kidneys were statistically diminished in BDL-rats as compared with controls (C, n=7; 35.0+/-2.3 mmHg ml(-1) min; BDL-rats, n=5; 23.8+/-0.7 mmHg ml(-1) min; p<0.02), without changes in EC15. Maximal relaxation induced by sodium nitroprusside in the phenylephrine (PHE)-pre-constricted renal vasculature in control preparations did not differ from that observed in BDL group (C: n=6; 49.5+/-2.3%). Values of EC50 were 1.26+/-0.07 microM (n=6) in control preparations and 0.34+/-0.03 microM (n=4) in kidneys from BDL-rats (p<0.001). Carbachol induced a biphasic relaxation of PHE-pre-constricted renal vasculature. No differences in maximal responses were found. EC50 value of the second phase in BDL group was significantly decreased compared to control preparations (C: n=6, 0.47+/-0.05 microM; BDL: n=6, 0.22+/-0.03 microM p<0.001). The present results show that the altered renal function after a short time post bile duct ligation is determined, at least in part, by increased release of arachidonic derivatives in vascular bed and tubular cells. At this stage of liver injury, the alteration in the renal vascular response to different vasoactive agents is remarkable.

Animals↗
PubMed2000

Cardiovascular responses of the taurine-depleted rat to vasoactive agents.

The objective of this study was to assess the effect of taurine-depletion on cardiovascular responses of rat to vasoactive agents. Male Wistar-Kyoto (WKY) rats were given either tap water (control) or 3% beta-alanine (taurine-depleted) for three weeks. Thereafter, mean arterial pressure (MAP) and heart rate of the freely moving animal were measured in response to vasoactive agents. Administration of phenylephine (5-40 microg/kg/min; i.v.) resulted in a similar and significant increase in MAP but a reduction in heart rate in both control and taurine-depleted groups. On the other hand, administration of sodium nitroprusside (15-300 microg/kg/min; i.v.) elicited a similar and significant reduction in MAP but increased heart rate in both groups. Lack of a differential response to phenylephrine and sodium nitroprusside between the two groups suggests that baroreflex regulation of cardiovascular function is not adversely affected by taurine-depletion. Administration of angiotensin II (0.1-3.0 microg/kg/min; i.v.) resulted in a dose-related increase in the pressor response and a decrease in heart rate in both groups. However, angiotensin II-induced pressor response was reduced in the taurine-depleted compared to the control rats (p < 0.05); heart rate was similarly reduced in both groups. Acute exposure to beta-alanine (3 g/kg; i.v., 30-minutes) did not alter angiotensin II-induced hemodynamic responses. Similarly, incubation of aortic rings with beta-alanine (40mM, 30 minutes) did not affect the contractile responses to angiotensin II. The results suggest that beta-alanine, per se, does not affect angiotensin II-induced responses in rat. However, beta-alanine-induced taurine depletion is associated with a reduction in the pressor response to angiotensin II without impairing baroreflex function.

Angiotensin II↗
PubMed1994

[Tumor microvascular bed and its reactivity to vasoactive agents: measurement of tissue blood flow and patho-morphological study].

Structural characteristics of tumor microvascular bed and its reactivity to vasoactive agents were studied by histological and ultrastructural examination and tissue blood flow measurement. The results showed that newly formed vessels in the tumor tissue consisted of a single layer of endothelial cells with multi-layer basement membranes and a few pericytes. Smooth muscle cells and nerve endings were absent. The tissue blood flow in highly proliferative parts of tumors was relatively constant and not influenced by tumor size, even though the distribution of neovasculature in tumor tissue was very uneven in distribution. The only vasoactive agent which can selectively increase the tumor blood flow was angiotensin II, whereas other adrenergic vasoconstrictors did not show this action.

Angiotensin II↗
PubMed2000

Risk factors for an early increase in dose of vasoactive agents for intracavernous pharmacotherapy.

AIMS: This study was to identify factors that influence the early increase in the dose of intracavernous vasoactive agents to maintain erection for satisfactory intercourse and to elucidate when the dose increase would begin. METHODS: Seventy-nine patients using intracavernous pharmacotherapy with tri-mix (PGE(1), papaverine, and phentolamine) over a 3- to 4-year period were enrolled. At 3-month intervals, patients were questioned about changes in dose to maintain erection for satisfactory intercourse and frequency of injection, and underwent examination of the penis. The patients were divided into 2 groups: group A, dose increase of > or = 20% after initiating home therapy, and group B, no change or an increase in dose < 20%. RESULTS: A significant increase (p < 0.01) in dose was started 2-3 years after initiating pharmacotherapy. The initial doses of group A at 2-3 and 3-4 years were significantly higher than those of group B (p < 0.01). There were no significant differences in the age of the patients, duration of erectile dysfunction, incidence of accompanying vascular risk factors, frequency of injection, or incidence of fibrous plaques between group A and group B, both at 2-3 and 3-4 years. CONCLUSION: The initial dose of intracavernous vasoactive agents (tri-mix) may be a unique risk factor for the early increase in dose to maintain erection for satisfactory intercourse.

Adult↗
PubMed1983

Pharmacological observations of plasminogen activator release caused by vasoactive agents in isolated perfused pig ears.

Influences of vasoactive agents on plasminogen activator release (PA release) and perfusion pressure (PP) were studied in isolated perfused pig ears. The pig ear was perfused with oxygenated Tyrode's solution, pH 7.4, at 37 degrees C via the main artery and the perfusate from the veins was collected at 2-min intervals. The drug was injected into a rubber tube connected in the front of arterial cannula, and the fibrinolytic activity in the collected perfusate was measured by the fibrin plate method. Acetylcholine, bradykinin, and histamine enhanced PA release in a dose-dependent fashion (0.1-3.0 micrograms). Purified human thrombin also enhanced PA release in a dose-dependent fashion (1.5-12 U). In coronary vasodilators, dilazep caused a dose-dependent increase of PA release (10-100 micrograms) and dipyridamole caused a slight increase at a dose of 300 micrograms. However, nitroglycerin, papaverine, diltiazem, and trapidil did not exert any effects on PA release and neither did adenosine and ATP. Vasoconstricting agents, namely, epinephrine, norepinephrine, phenylephrine, and serotonin exerted hypertensive effects in a dose-dependent fashion (0.1-3.0 micrograms); however, they did not cause measurable increases of PA release. These results suggest that vasodilating substances may be essential for the enhancement of PA release from vascular bed.

Animals↗
PubMed1985

Response of the forelimb vasculature to vasoactive agents: effects of ouabain.

The effect of the local intra-arterial infusion of ouabain (11.8 micrograms/min.) on the response of the forelimb to vasoactive agents was examined. In seven dogs, bolus injections of CaCl2, MgSO4, KCl, norepinephrine, adenosine, acetylcholine, PGE1 and saline were made into the forelimb perfused at constant flow before and three times during ouabain infusion. Ouabain blocked potassium vasodilation and changed the response to CaCl2 from vasoconstriction to vasodilation. The response of the forelimb to the other vasoactive agents was initially unaffected by ouabain but with time the forelimb vasculature became less sensitive to all agents studied. These changes were not seen in a series of 5 saline infused control animals. In a third series of animals steady-state dose responses to CaCl2, Ca-gluconate and KCl were explored by infusing solutions intrabrachially at three dosages. Before ouabain, forelimb resistance increased as a function of Ca++ and decreased as a function of K+. Ouabain completely blocked potassium vasodilation and on the average blocked Ca++ vasoconstriction although a number of animals evidenced vasodilation to Ca++ during ouabain infusion. These data indicate that K+ vasodilation is Na+, K+-ATPase dependent and that Na+, K+-ATPase inhibition unmasks a vasodilatory action of locally applied Ca++.

Alprostadil↗
PubMed2003

Serum vasoactive agents in lead-treated rats.

BACKGROUND: It is still unknown whether mechanisms of the hypertensinogenic effect of lead include changes in synthesis or release of vasoactive agents. This question is essential with regard to lead dissemination in the human environment as well as to frequent occurrence of arterial hypertension. OBJECTIVES: The aim of the study was to evaluate the effect of chronic exposure to lead on the vasoactive agents in blood in relation to redox system activity in vessel walls and to disturbances in homeostasis of essential metals. Using lead in double small, hypertensive doses we tried to estimate whether this effect dependents on the degree of lead exposure. METHODS: The study was performed on the male Buffalo rats which were given lead in drinking water, 50 or 100 ppm (lead acetate dissolved in distillate water) for 12 weeks. Control rats were given distillate water. Rats were fasted starting the night before the experiment, and the next day were anesthetized intramuscularly with ketaminum at a dose of 300 mg/kg body weight. The abdomen was opened and the aorta was isolated. Blood samples were drawn from heart, abdominal and thoracic aorta and then kidneys were excised. Serum nitric oxide and prostaglandin PGF(2alpha) concentrations were measured using R&D systems, and the plasma endothelin-1 level with enzymoimmunoassay; 5% homogenates of aorta were prepared from thoracic fragment in saccharose buffer. Lipid peroxides in homogenates were determined colorimetrically and glutathione was measured using colorimetric assay BIOXYTECH GSH-400. The concentration of metals (lead, copper and zinc) in blood and aorta were determined with a plasma spectrometer. RESULTS: The study shows different changes in toxicological and biochemical status, depending on the dose of metal. Mean serum nitric oxide concentration was higher in rats treated with lead in a dose of 50 ppm (p < 0.01) or 100 ppm (p < 0.001) than in the control group. The plasma endothelin-1 level was lower in rats given lead in a dose of 50 ppm (p < 0.05) than in controls, whereas serum prostaglandin PGF(2alpha) concentration was similar in all animals. Glutathione concentration in aorta was higher in both groups of rats treated with lead (p < 0.001) in comparison to controls. There were positive linear dependencies between: (a) blood lead and serum nitric oxide; (b) aorta glutathione and serum nitric oxide; (c) copper in aorta and glutathione in aorta; (d) serum zinc and plasma endothelin-1 concentrations. CONCLUSIONS: It was concluded, that lead in small doses increases synthesis and/or releases nitric oxide and its concentration in serum. This effect of lead is probably connected with the augmented production of glutathione in vessel walls. Additionally, lead in a dose of 50 ppm provokes the decrease in the level of plasma endothelin-1, probably through the decreased level of serum zinc. We suppose that the mechanisms responsible for the vascular effect of lead differ even within the range of hypertensive doses.

Animals↗