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Z Zukowska-Grojec

Publications and source records attributed to Z Zukowska-Grojec.

69 records · Page 4Linked to original sources
PubMed1983

Effect of desipramine and cocaine on plasma norepinephrine and pressor responses to adrenergic stimulation in pithed rats.

Sympathetic neuronally released norepinephrine appears to act at intrajunctional alpha 1-adrenoceptors, whereas administered norepinephrine acts mostly at extrajunctional alpha 2-adrenoceptors. We examined the effects of inhibition of neuronal uptake of norepinephrine by desipramine (0.3 mg/kg iv) and cocaine (5 mg/kg iv) on the pressor effects and on plasma norepinephrine levels in pithed rats after the administration of norepinephrine (0.1, 0.3, and 1.0 micrograms/kg iv) or during stimulation of sympathetic outflow (0.1, 0.3, and 1.0 Hz at 50 V for 1 minute). Desipramine and cocaine potentiated the cardiovascular effects of administered norepinephrine to a greater extent than they potentiated the effects of sympathetic stimulation. Plasma levels of norepinephrine during sympathetic stimulation or after iv administration of norepinephrine were increased significantly after either desipramine or cocaine. The cardiovascular effects of sympathetic stimulation, but not of exogenous norepinephrine, were reduced in adrenomedullectomized rats compared to intact rats. In adrenomedullectomized rats, desipramine potentiates the pressor responses and enhances the increase in plasma norepinephrine levels during sympathetic stimulation to the same extent as in intact pithed rats. The preferential potentiation of administered norepinephrine by uptake inhibition is most likely due to enhancement of accessibility of circulating norepinephrine to otherwise inaccessible intrajunctional alpha 1-adrenoceptors. The higher concentrations of norepinephrine in the region of the nerve-ending limit release of the neurotransmitter by feedback inhibition via presynaptic alpha 2-adrenoceptors, thereby masking potentiation by uptake inhibition of the postsynaptic responses to sympathetic stimulation.

Animals↗
PubMed1983

Leukotriene D4-induced hypotension is reversed by thyrotropin-releasing hormone.

Injection of leukotriene D4 (LTD4, 20 micrograms/kg, i.a.) to conscious spontaneous hypertensive (SHR) rats produces a short-lasting pressor and tachycardic response followed by prolonged hypotension and bradycardia. Plasma norepinephrine and epinephrine were elevated at the peak pressor/tachycardic phase as well as at the hypotensive phase. Injection of thyrotropin-releasing hormone (TRH, 2 or 5 mg/kg) at the peak of the LTD4-induced hypotension resulted in prompt reversal of the hypotension and bradycardia in a dose-related manner. Naloxone (5 mg/kg) had no effect on blood pressure and heart rate of LTD4-treated SHR rats. Pretreatment with TRH (5 mg/kg) did not prevent the depressor effect of LTD4, but attenuated the bradycardic effect of this leukotriene. In addition, TRH had no effect on LTD4-induced hypotension in the pithed SHR rat. These results suggest that TRH might exert beneficial effects in hypotensive states mediated by leukotrienes or other mediators of anaphylactic reactions.

Animals↗
PubMed1983

Effects of chronic arachidonate on blood pressure of spontaneously hypertensive rats.

Three weeks of treatment with arachidonic acid (250 mg/kg/day, s.c.) produced an antihypertensive effect in 16 week-old spontaneously hypertensive rats (SHR) as compared with vehicle treated rats. Indomethacin (4 mg/kg, s.c. B.I.D.), given concurrently with arachidonate, abolished the antihypertensive effect. Plasma catecholamines were not altered by the arachidonate treatment, but blood pressure increments after spinal cord stimulation or after intravenous administration of norepinephrine and angiotensin II in the pithed rat were diminished. Increments in plasma catecholamines in response to spinal cord stimulation were similar in both groups of pithed rats. These data demonstrate the antihypertensive effect of arachidonic acid in SHR with established hypertension. This beneficial effect seems to be mediated through cyclooxygenase metabolites, and might be related to reduced responsiveness of peripheral blood vessels to pressor stimuli.

Angiotensin II↗
PubMed1983

6-Fluorocatecholamines as false adrenergic neurotransmitters.

In the present study 6-fluoronorepinephrine (6F-NE) is shown to be formed from 6-fluorodopamine (6F-DA) in vivo. The beta-hydroxylated fluorocompound is taken up by and stored in the adrenergic nerve terminals and can be released during sympathetic nerve stimulation. In the heart, the turnover rate of the exogenously administered 6F-NE was about the same as that of tritium-labeled norepinephrine. In the central nervous system, 6F-DA can be taken up by the nigrostriatal neurons. After depolarization of the dopaminergic neurons by potassium, 6F-DA is released along with the endogenous dopamine. Systemic administration of 6F-NE to the pithed rats produces dose-dependent increases in blood pressure but does not increase the heart rate. The vasopressor potency of 6F-NE is about the same as that of l-norepinephrine, about 2-fold greater than that of dl-norepinephrine. Combined treatment with yohimbine and prazosin antagonizes completely the vasopressor effect of 6F-NE. The duration of the pressor response to 6F-NE was twice that of dl- or l-norepinephrine. The present study indicates that 6-fluorocatecholamines fulfill the criteria for adrenergic false transmitters and may be useful in positron emission tomographic scanning for mapping specifically the adrenergic nervous system in the brain or in the peripheral sympathetic nerves.

Animals↗
PubMed1982

Cardiovascular and sympathetic effects of l-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine in conscious SHR and WKY rats.

Injections of 1-)-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (alkylacetyl-GPC, 0.2-5.0 nmol/300 g body weight) induced dose-related hypotension and tachycardia in spontaneous hypertensive (SHR) and normotensive control (WKY) rats. The hypotension that developed was more pronounced in SHR than in WKY rats and was unchanged by indomethacin pretreatment. Plasma norepinephrine (NE) and epinephrine (EPI) levels were markedly increased at the time of maximal hypotension (2 min after injection of alkylacetyl-GPC); plasma EPI (but not NE) was higher in the SHR than in WKY animals. Plasma levels of TXB2, but not 6-keto-PGF 1 alpha, increased in both groups; the increase was more pronounced in SHR than in WKY rats. In pithed SHR rats, alkylacetyl-GPC caused only short lasting hypotension without any effect on heart rate or circulating levels of NE or EPI. These data suggest that there is an increased vascular sensitivity to alkylacetyl-GPC in SHR rats and activation of thromboxane-generating elements in both SHR and WKY rats.

Animals↗
PubMed1982

Leukotriene D4: cardiovascular and sympathetic effects in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats.

Leukotriene D4 (1--20 micrograms/kg i.a.) administered to conscious spontaneously hypertensive rats (SHR) and WKY rats caused acute elevation of blood pressure in both groups, but only in SHR a prolonged hypotensive period followed the hypertensive event. SHR rats had tachycardia during the hypertensive phase and relative bradycardia during the hypotensive phase which was more pronounced and prolonged than in WKY rats. In SHR rats only, plasma epinephrine and norepinephrine were elevated (6- and 3-fold, respectively) at the peak of the hypertensive period. Pretreatment of SHR rats with indomethacin (5 mg/kg) potentiated the LTD4-induced pressor response and shortened the hypotensive-bradycardic effect of LTD4. This same biphasic, dose-dependent response to LTD4 (1--20 micrograms/kg i.v.) was present in pithed SHR rats. Therefore, a direct action of LTD4 on vascular smooth muscle and heart is suggested. In all WKY rats and some SHR rats, a bradycardic effect of LTD4 resulted from sinus bradycardia, whereas in pithed SHR rats impaired conduction varying from transient second degree atrioventricular block to complete heart block was observed. Electrocardiographic signs of ischemia were seen only in LTD4-injected, pithed SHR rats. These results suggest fundamental differences between SHR and WKY rats in regard to their sensitivity to lipoxygenase products.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

Cardiovascular effects of leukotriene D4 in SHR and WKY rats.

Leukotriene D4 (LTD4, 0.8-4 micrograms/kg i.a.) increased blood pressure and heart rate of conscious SHR and WKY rats. LTD4, 20 micrograms/kg (i.a.), caused a short lasting increase in blood pressure and heart rate in WKY. In SHR, LTD4, 20 micrograms/kg (i.a.) caused a triphasic effect: hypotension and bradycardia (0.5-1 min), hypertension and tachycardia (2-5 min) and prolonged hypotension and bradycardia (5-180 min). Leukopenia was observed after LTD4, 20 micrograms/kg in both groups of rats but platelets count was unaffected. These results show that SHR are mor sensitive than WKY to the hypotension-bradycardia effect of LTD4.

Animals↗
PubMed1977

Metabolic and hormonal studies in patients with essential hypertension.

In 106 patients with essential hypertension and different plasma renin activity several hormonal and metabolic factors were studied: urinary excretion of catecholamines, blood levels of cholesterol and triglycerides, levels of glycaemia and insulinaemia after glucose load and plasma fibrinolytic activity. The plasma renin activity in 46.2 percent of patients was normal, whereas in 25.5 percent it was low, and in 28.3 percent it was high. In patients with high plasma renin activity the excretion of noradrenaline and adrenaline was relatively high while that of dopamine was low. Significantly lower triglyceride levels were found in patients with low plasma renin activity in comparison with those with high and normal plasma renin activity. There was also a statistically significant difference in the euglobulin lysis time which was shorter in patients with low and longest in patients with normal plasma renin activity. The results of the study show that patients with different plasma renin activity may also differ in some hormonal and metabolic values.

Adult↗
PubMedDate not supplied

Effect of dermorphin and morphine on the sympathetic and cardiovascular system of the pithed rat.

Dermorphin is a recently discovered opioid peptide which is unique in having a D-amino acid in its sequence. Dermorphin binding sites have been shown in central and peripheral organs and central administered dermorphin produces profound autonomic responses. The purpose of this study was to examine the effect of intravenous dermorphin on heart rate and blood pressure of the pithed rat in basal condition and in response to controlled sympathetic stimulation. Also, since dermorphin is a selective mu-receptor agonist, its effects were compared to morphine, an opiate selective for mu receptors. Dermorphin (0.0001-10 mumol/kg, i.v) or morphine (1-10 mg/kg) had no effect on basal heart rate or blood pressure and failed to modify sympatho-adreno-medullary evoked pressor and tachycardic responses. Furthermore, dermorphin or morphine did not affect the increase in plasma norepinephrine and epinephrine in response to spinal cord stimulation. It is concluded that the dermorphin and morphine have no direct peripheral effects on heart rate or blood vessel tone nor do these mu-receptor agonists have any effect on norepinephrine and epinephrine release from the sympathetic nerves and the adrenal medulla in the rat.

Animals↗
PubMedDate not supplied

Mitogenic effect of neuropeptide Y in rat vascular smooth muscle cells.

Neuropeptide Y (NPY) is a vasoconstrictor released with norepinephrine from perivascular sympathetic nerves. Since sympathetic nerves appear to play a role in vascular smooth muscle cell (SMC) hypertrophy, we studied the effects of NPY on proliferation of cultured rat aorta- and vena cava-derived SMC. Both cell types displayed high-affinity NPY binding sites with displacement characteristics of [Pro34]NPY > NPY(13-36) > NPY(18-36) in aorta and [Pro34]NPY = NPY(13-36) = NPY(18-36) in the vena cava. Incubation with NPY (50-1000 nM) for 48 h increased by up to twofold cell number and [3H]-thymidine incorporation in both cell types (aortic more sensitive to NPY than venous). Following incubation with NPY, the disappearance of NPY immunoreactivity (-IR) from media was markedly delayed in the presence of SMC, and cell content of NPY-IR increased in a dose-dependent manner, indicating that SMC either diminish degradation of the peptide (possibly by internalization) or secrete endogenous NPY (or both). Structure-activity relationship studies with NPY(18-36) indicated involvement of Y1 receptors in mitogenesis. Thus, NPY has a mitogenic effect (probably mediated by Y1 receptors) and, therefore, may be a sympathetic trophic factor involved in vascular hypertrophy.

Animals↗
PubMedDate not supplied

Effect of desipramine on the effects of alpha-adrenoceptor inhibitors on pressor responses and release of norepinephrine into plasma of pithed rats.

The role of neuronal uptake inhibition on the efficiency of alpha 1- and alpha 2-antagonists in inhibiting pressor responses and the release of plasma catecholamines in pithed rats were studied. Prazosin, in doses which selectively blocked alpha 1-adrenoceptors (0.01-0.1 mg/kg), was more effective than yohimbine, a relatively selective alpha 2-antagonist, in inhibiting stimulation-induced pressor responses. Yohimbine (0.1-1 mg/kg) potentiated or did not alter the pressor responses to stimulation, whereas it blocked pressor responses to administered norepinephrine (NE) more effectively than did prazosin. Inhibition of uptake by desipramine (DMI), 0.3 mg/kg, did not affect prazosin inhibition of stimulation-induced pressor responses though it increased NE overflow into circulation. In yohimbine-treated rats, DMI potentiated significantly (p less than 0.001) both pressor and NE responses to stimulation. DMI partially reversed prazosin inhibition of pressor response to administered NE (p less than 0.001) and potentiated the response in yohimbine-treated rats (p less than 0.01). The results are consistent with the view that endogenously released NE acts at intrajunctional alpha 1-adrenoceptors, whereas exogenous NE acts predominantly at extrajunctional alpha 2-adrenoceptors. The neuronal uptake site appears to be functionally (and perhaps anatomically) located outside the synaptic cleft, between intrajunctional alpha 1-postsynaptic receptors and extrajunctional alpha 2-adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Cardiovascular and sympathetic responses to chronic arachidonate in SHR and WKY rats.

In rats between the ages of 4 and 12 or 14 weeks, repeated daily subcutaneous administration of arachidonate (AA) at a dose of 50 or 200 mg/kg significantly retarded the development of hypertension in spontaneously hypertensive rats (SHR) but did not alter the normal age-related increase in blood pressures (BP) of normotensive (WKY) rats. Heart rates (HR) and plasma levels of norepinephrine (NE), but not epinephrine, were lower in AA-treated SHR than in saline-treated animals. AA-treated SHR and WKY gained less weight than the saline-treated controls. In pithed AA-treated SHR, stimulation of the sympathetic outflow (50 V, for 1 minute at 0.3 or 3.0 Hz) and intravenous administration of NE (0.3 or 3.0 g/kg) evoked smaller pressor responses than in saline-treated controls, but the stimulation-evoked increases in plasma catecholamines were unchanged by AA treatment. These results indicated that, in SHR, chronic AA treatment reduces BP by mechanisms that do not directly affect NE release from sympathetic nerves. There appears to be both reduced central nervous system activation of the sympathetic outflow and diminished responses to peripheral sympathetic stimulation and exogeneous NE which may be secondary to the reduced vascular hypertrophy that usually accompanies the development of high BP in SHR.

Animals↗
PubMedDate not supplied

Role of catecholamines and vasopressin in cardiovascular responses to bilateral dorsolateral transection of the medulla oblongata in the rat.

The role of sympathetic and other pressor systems in the development of fulminant hypertension induced by baroreceptor deafferentation is still unclear. We studied the effects of acute hypertension produced by bilateral dorsomedullary knife cuts lateral to the nucleus tractus solitarii (DMK-cut) on plasma norepinephrine (NE), epinephrine (E), and vasopressin (VP) in conscious, tail-artery-cannulated rats. In saline-pretreated (SAL) rats, DMK-cut caused a significant (p less than 0.001) rise in mean blood pressure (MAP, +68 +/- 3 mm Hg), heart rate (HR, +97 +/- 19 bpm), NE (+2.5 +/- 0.3 ng/ml), E (+2.7 +/- 0.4 ng/ml), and VP (+115 +/- 34 pg/ml) compared to sham-operated rats. Neither sympathetic blockade with chlorisondamine (CHLO, 10 mg/kg, s.c.) nor elimination of the pressor effects of VP by use of Brattleboro rats or the VP pressor antagonist resulted in a maximal MAP response significantly different from that in the SAL + DMK-cut group. However, CHLO-pretreatment of Brattleboro rats completely abolished the increase in MAP and HR. It is suggested that the bilateral DMK-cut causes acute hypertension, probably due to the abolition of baroreceptor reflexes by central interruption of neural connections of the nucleus tractus solitarii. It appears that both the increased sympathoadrenomedullary activity and VP release normally contribute to this hypertension; however, either one is sufficient to sustain the elevated blood pressure.

Animals↗
PubMedDate not supplied

Overall and regional hemodynamic effects of leukotriene D4 in spontaneously hypertensive rats.

Leukotriene D4, a constituent of slow-reacting substance of anaphylaxis, elicits a pressor response followed by hypotensive shock in spontaneously hypertensive rats but not in other rats. Hemodynamic mechanisms underlying this pattern in spontaneously hypertensive rats, pithed and vagotomized to eliminate circulatory reflexes, were studied using radiolabeled microspheres. One minute after leukotriene D4 administration (20 micrograms/kg i.v.), mean arterial pressure increased by 54 mm Hg, total peripheral resistance index increased by 68%, heart rate decreased by 34 beats/minute, and cardiac index was unchanged. Profound reductions of blood flow and increases of vascular resistance in the hepatosplanchnic area, skeletal muscles, and skin also occurred. Five minutes later, mean arterial pressure remained elevated (+35%), hematocrit rose (+17%), and total peripheral resistance index increased, which offset 40% decreases in cardiac and stroke volume indices. Ten minutes after leukotriene D4 administration, during hypotension, cardiac and stroke volume indices and blood flow to all vascular beds declined further while total peripheral resistance index and hematocrit (+28%) continued to rise. In Wistar-Kyoto rats, administration of leukotriene D4 caused less of a pressor response (+34 mm Hg) because vascular resistance was increased only in skeletal muscles, which was followed by a slight hypotension without any significant changes in cardiac and stroke volume indices, total or regional vascular resistance, and hematocrit. Thus, in spontaneously hypertensive rats the leukotriene D4-induced pressor response appears to be caused by generalized vasoconstriction, and the subsequent hypotension appears to result not from vascular collapse but from reduced cardiac output.

Adrenal Glands↗