Biomedical subjects

Z Zukowska-Grojec

Publications and source records attributed to Z Zukowska-Grojec.

At least 37 records · Page 2Linked to original sources

PubMed1993

Influence of cigarette smoking on human autonomic function.

BACKGROUND: Although cigarette smoking is known to lead to widespread augmentation of sympathetic nervous system activity, little is known about the effects of smoking on directly measured human sympathetic activity and its reflex control. METHODS AND RESULTS: We studied the acute effects of smoking two research-grade cigarettes on muscle sympathetic nerve activity and on arterial baroreflex-mediated changes of sympathetic and vagal neural cardiovascular outflows in eight healthy habitual smokers. Measurements were made during frequency-controlled breathing, graded Valsalva maneuvers, and carotid baroreceptor stimulation with ramped sequences of neck pressure and suction. Smoking provoked the following changes: Arterial pressure increased significantly, and RR intervals, RR interval spectral power at the respiratory frequency, and muscle sympathetic nerve activity decreased. Plasma nicotine levels increased significantly, but plasma epinephrine, norepinephrine, and neuropeptide Y levels did not change. Peak sympathetic nerve activity during and systolic pressure overshoots after Valsalva straining increased significantly in proportion to increases of plasma nicotine levels. The average carotid baroreceptor-cardiac reflex relation shifted rightward and downward on arterial pressure and RR interval axes; average gain, operational point, and response range did not change. CONCLUSIONS: In habitual smokers, smoking acutely reduces baseline levels of vagal-cardiac nerve activity and completely resets vagally mediated arterial baroreceptor-cardiac reflex responses. Smoking also reduces muscle sympathetic nerve activity but augments increases of sympathetic activity triggered by brief arterial pressure reductions. This pattern of autonomic changes is likely to influence smokers' responses to acute arterial pressure reductions importantly.

Adult↗

PubMed1992

Blood pressure responses to sucrose ingestion in four rat strains.

Among four strains examined, spontaneously hypertensive rats (SHR) show a marked (20 mm Hg, P less than .01) systolic blood pressure elevation (SBP), Sprague-Dawley (SD) and Wistar-Kyoto (WKY) rats developed a moderate elevation (8 mm Hg, P less than .01), and a normotensive Wistar rat (WAM) had a lesser SBP elevation (6 mm Hg, P = NS) after excess sucrose ingestion. The SBP elevations found in SHR were noted at 2 and 4 weeks after starting the dietary treatments. Corresponding with SBP changes, plasma renin activity (PRA), aldosterone, and neuropeptide Y (NPY) concentrations all decreased with the high sucrose-low protein diet compared to the low sucrose-high protein diet, while circulating insulin levels were unchanged. Although norepinephrine (NE) and epinephrine (E) excretion tended to be higher in the rats eating the high sucrose-low protein food, the differences were not statistically significant. The differences in these parameters could influence the SBP in SHR, SD, and WKY, but virtually similar qualitative and quantitative blood and urinary findings were found in WAM, a strain of rat that showed no significantly increased SBP. Removing one kidney increases the CHO-induced SBP response of WKY to levels comparable to those seen in SHR, converting a moderate responder to a highly sensitive one. We conclude that under well-controlled conditions there are obvious differences in the SBP response to the macronutrients in the diets of various rat strains and that SHR possess some intrinsic mechanism(s), most likely associated with renal metabolism, which make this strain more sensitive to refine CHO-induced SBP elevations.

Administration, Oral↗

PubMed1992

Cardiovascular effects of omega-conopeptides in conscious rats: mechanisms of action.

We examined the effects of omega-conopeptides, a novel class of neuronal voltage-gated calcium channel antagonists, on hemodynamic responses in rats. Intravenous (i.v.) injections of SNX-111 (omega-conopeptide MVIIA) dose-dependently decreased arterial blood pressure (BP) in conscious rats. Intracerebroventricular (i.c.v.) SNX-111 injections (580 pmol) tended to increase BP and, after an initial decrease, to increase heart rate (HR). The dose-response curve for SNX-111 administered i.v. in conscious rats was biphasic. Beginning at subdepressor doses, SNX-111 caused a long-lasting blockade of pressor responses elicited by sympathetic nerve stimulation in pithed animals but did not prevent increases in BP evoked by exogenously administered norepinephrine (NE). Pretreatment of rats with histamine antagonists partially blocked the hypotensive effects of the higher (870 and 2,900 nmol/kg) doses of SNX-111. Substitution of alanine for arginine at position 10 ([Ala10]-MVIIA) markedly attenuated the histamine-mediated component of the vasodepressor response. Together, these findings indicate that SNX-111 administered i.v. decreases systemic BP by a combination of blockade of sympathetic neurotransmission and mast cell degranulation; the latter function appears to be dependent on the arginine residue in position 10 of the amino acid sequence of SNX-111.

Amino Acid Sequence↗

PubMed1991

C-terminal neuropeptide Y fragments are mast cell-dependent vasodepressor agents.

Neuropeptide Y (NPY) is a well-established vasopressor agent present in sympathetic perivascular nerves. Recently, it was found that high doses of the peptide cause a biphasic pressor-depressor response upon intravenous administration. We now report that C-terminal NPY fragments (NPY-(18-36) and NPY-(22-36] given intravenously to conscious or pithed (areflexive) male Sprague-Dawley rats mimic the depressor component of the NPY-(1-36) response while displaying very low pressor activity. Additionally, we have found that the depressor component is blocked by the histamine H1-antagonist, mepyramine. Since the fragment, NPY-(22-36), was equipotent with NPY in inducing histamine release from isolated peritoneal mast cells, we conclude that short C-terminal NPY fragments, like NPY itself, act on mast cells to initiate histamine-mediated cardiovascular actions. Such actions may conceivably be accounted for by the abundance of positively charged amino acid residues in the C-terminus. Moreover, these fragments have little affinity for vascular NPY receptors, as indicated by their poor ability to displace iodinated NPY or peptide YY (PYY) from specific binding sites on vascular smooth muscle cells derived from rat aorta. In conclusion, we propose that short C-terminal NPY fragments, which contain several positively charged amino acid residues, retain the ability of NPY to release histamine from rat mast cells while being essentially devoid of direct vascular motor activity.

Animals↗

PubMed1991

Re-evaluation of the effects of neuropeptide Y on aggregation of human platelets.

Several studies have shown that platelets are a major source of circulating neuropeptide Y (NPY) immunoreactivity in rats, but the effects of this vasoconstrictor peptide on platelets are not well-defined. Recently, it was reported that porcine NPY was an inhibitor of in vitro human platelet aggregation induced by epinephrine, an observation which would have important implications regarding platelet-vascular interactions during states involving platelet activation and thrombosis. Thus, we undertook the present studies, in an attempt to confirm the earlier report, and to extend those observations to human NPY. In contrast to the recent report, we found no inhibitory effect of either human or porcine NPY on epinephrine- or collagen-induced aggregation of human platelets from normal subjects. Likewise, specific NPY Y-1 and Y-2 agonists had no direct or indirect action on platelet aggregation. Finally, the effect of human NPY on intraplatelet cAMP was measured. The peptide had no effect on either basal or iloprost-stimulated cAMP levels. We hypothesize that the role of NPY in the platelet-vascular interaction is in promoting vasoconstriction associated with platelet aggregation, and does not include inhibition of further thrombosis.

Adult↗

PubMed1991

Cardiovascular, neuropeptide Y, and adrenergic responses in stress are sexually differentiated.

Cardiovascular and sympatho-adrenomedullary responsiveness at rest and during stress were studied in weight-matched, sexually mature male and female rats. At rest, although there were no sex differences in cardiovascular parameters, females had two-fold higher plasma levels of norepinephrine (NE) and epinephrine. Resting plasma levels of neuropeptide Y-immunoreactivity (NPY-ir, a putative sympathetic cotransmitter and a vasoconstrictor) were similar in both sexes. Stresses of handling and cold (4 degrees C) water exposure induced greater pressor and tachycardic responses in males than in females. Males but not females exhibited a protracted recovery from the stress-induced pressor responses and a 2-fold increase in plasma NPY-ir suggesting that NPY release is sexually differentiated. Only in males, low basal plasma NE and NPY-ir levels inversely correlated with greater cold-induced pressor responses. Furthermore, in areflexic pithed rats, pressor adrenergic and NPY responses were greater in males than in females suggesting the possibility of "down"-regulation of vascular adrenergic receptors in females (due to elevated circulating catecholamines) and "up"-regulation of NPY and adrenergic receptors in males.

Adrenergic Fibers↗

PubMed1990

Biphasic blood pressure response to neuropeptide Y in anesthetized rats.

The effects of neuropeptide Y (NPY) on systemic arterial blood pressure and heart rate were studied in anesthetized intact and pithed rats. I.v. doses of NPY (0.3-30 nmol/kg) raised the mean arterial blood pressure dose dependently. At doses of greater than or equal to 3.0 nmol/kg, the initial pressor response was followed by a dose-dependent fall in blood pressure in intact and pithed rats. The depressor response was accompanied 1-2 min after the NPY injection by a slight increase in heart rate in pithed rats but not in intact rats, and 10 min after the injection by a decrease in heart rate in intact rats. After repeated injections of NPY, the depressor effect vanished, whereas the integrated pressor response over time was markedly enhanced. After pretreatment with the histamine H1-receptor antagonist, mepyramine, or with the histamine liberator, compound 48/80, the pressor response to NPY remained but the depressor response disappeared. We suggest that the marked fall in blood pressure can be attributed to NPY-evoked histamine release from mast cells.

Anesthesia↗

PubMed1990

Neuropeptide Y receptor subtypes, Y1 and Y2.

Heterogeneity among NPY (and PYY) receptors was first proposed on the basis of studies on sympathetic neuroeffector junctions, where NPY (and PYY) can exert three types of action: 1) a direct (e.g., vasoconstrictor) response; 2) a postjunctional potentiating effect on NE-evoked vasoconstriction; and 3) a prejunctional suppression of stimulated NE release; the two latter phenomena are probably reciprocal, since NE affect NPY mechanisms similarly. It was found that amidated C-terminal NPY (or PYY) fragments, e.g., NPY 13-36, could stimulate selectively prejunctional NPY/PYY receptors, which were termed Y2-receptors. Consequently, the postjunctional receptors which were activated poorly by NPY/PYY fragments, were termed Y1-receptors. Later work has indicated that the Y2-receptor may occur postjunctionally in selected sympathetic effector systems. The central nervous system appears to contain a mixture of Y1- and Y2-receptors as indicated by functional as well as binding studies. For instance, NPY and NPY 13-36 produced diametrically opposite effects on behavioral activity, indicating the action of the parent peptide on two distinct receptors. Cell lines, most importantly neuroblastomas, with exclusive populations of Y1- or Y2-receptors, have been characterized by binding and second messenger studies. In this work, selective agonists for the two receptor subtypes were used. Work of many investigators has formed the basis for subclassifying NPY/PYY effects being mediated by either Y1- or Y2-receptors. A preliminary subclassification based on effects of NPY, PYY, fragments and/or analogs is provided in Table 6. It is, however, to be expected that further receptor heterogeneity will be revealed in the future. It is argued that mast cells possess atypical NPY/PYY receptors. The histamine release associated with stimulation of the latter receptors may, at least in part, underlie the capacity of NPY as well as of short C-terminal fragments to reduce blood pressure. Fragments, such as NPY 22-36, appear to be relatively selective vasodepressor agents because of their weak vasopressor properties.(ABSTRACT TRUNCATED AT 400 WORDS)

Calcium↗

PubMed1990

Norepinephrine and neuropeptide Y: vasoconstrictor cooperation in vivo and in vitro.

Norepinephrine (NE)-evoked vasoconstrictor and pressor responses are reduced after prolonged exposure; such desensitization is observed both clinically and experimentally. The vasoconstrictor neuropeptide Y (NPY) coexists with NE in perivascular sympathetic nerves, and the results of both in vivo and in vitro studies have indicated functional cooperation between NE and NPY. We propose that NPY becomes increasingly important in situations of high sympathetic activity associated with blunted NE responses. Prolonged NE infusion in conscious rats resulted in adrenergic desensitization; however, NPY administration restored the responsiveness to NE. In naive rats, NE greatly enhanced the pressor action of NPY. An analogous phenomenon was observed in the rabbit isolated pulmonary artery, which failed to respond to NPY unless preexposed to NE; this action of NE was only partly inhibited by conventional adrenoceptor and Ca2+ influx blockade. Conversely, NPY enhanced NE-evoked constriction, in particular when the alpha-adrenoceptor reserve was eliminated. It is proposed that threshold synergism, in part caused by converging stimulation of phospholipase C, accounts for much of the NPY/NE cooperativity. We conclude that 1) NPY and NE cooperate to produce vasoconstriction, both in vivo and in vitro; 2) NPY has the capacity to reverse adrenergic desensitization but not vice versa; 3) NE enhances NPY-evoked vasoconstriction, in part independently of conventional adrenoceptor blockade; 4) threshold synergism phenomena, but not "receptor-receptor interactions," account for (most of) the observed NPY/NE cooperation; and 5) when present, alpha-adrenoceptor reserve prevents the lowering of the NE threshold by NPY.

Adrenergic alpha-Agonists↗

PubMed1989

Plasma levels of catechols during reflexive changes in sympathetic nerve activity.

Relationships between changes in levels of catechols and directly recorded sympathetic nerve activity were examined using simultaneous measurements of renal sympathetic nerve activity and arterial and renal venous concentrations of norepinephrine (NE), dihydroxyphenylalanine (dopa), and dihyroxyphenylglycol (DHPG) during reflexive alterations in renal sympathetic nerve activity in anesthetized, adrenal-demedullated rats. Nitroprusside infusion increased renal sympathetic nerve activity by 90%, arterial levels of dopa by 96%, NE by 326%, and DHPG by 141%. Phenylephrine infusion increased arterial DHPG levels by 81% and decreased renal sympathetic nerve activity by 37% and NE levels by 26%; arterial dopa levels were unchanged. Ganglionic blockade by chlorisondamine (with concomitant phenylephrine infusion to maintain MAP) decreased renal sympathetic nerve activity by 65% and NE concentrations by 37%; arterial dopa concentrations were unchanged, and DHPG concentrations increased by 60%. Proportionate responses of arterial levels of NE were strongly related to proportionate changes in renal sympathetic nerve activity. Clearance of DHPG from arterial plasma was prolonged by phenylephrine-induced hypertension and by nitroprusside-induced hypotension. The results suggest that changes in arterial NE levels reflect changes in sympathetic activity; changes in dopa levels reflect changes in catecholamine biosynthesis; and changes in DHPG levels depend on reuptake of released NE and on hemodynamic factors affecting DHPG clearance.

Animals↗

PubMed1989

Opposite effects of chronic cortisol treatment on pre- and postsynaptic actions of clonidine in pithed rats.

1. Both clinical and experimental studies have shown that chronic elevation of plasma cortisol levels are attended by altered adrenergic receptor function. In the present study we examined the effects of chronic cortisol treatment (25 mg kg-1 day-1 for 7 days by minipumps) on the peripheral cardiovascular responses of pithed, adrenal demedullated vagotomized rats. 2. Chronic cortisol treated rats had higher basal diastolic blood pressures after being pithed, suggesting that sympathetic outflow is not required to sustain elevated peripheral resistance in glucocorticoid-induced hypertension. 3. Whereas alpha 1-adrenoreceptor-mediated diastolic blood pressure responses were unaltered, alpha 2-adrenoreceptor-mediated vasopressor responses were potentiated in pithed rats which were chronically treated with cortisol. 4. Elevation of plasma noradrenaline induced by the stimulation of the entire sympathetic outflow of pithed rats was not changed but the clonidine-induced presynaptic alpha 2-adrenoreceptor inhibition of noradrenaline release was attenuated by chronic cortisol treatment. 5. In conclusion, in adrenal demedullated pithed rats the responses mediated by peripheral pre- and postjunctional alpha 2-adrenoreceptors appeared to be affected oppositely after chronic cortisol treatment, suggesting that the pharmacologically homogeneous alpha 2-adrenoreceptor population may be modulated differently by chronic elevation of plasma glucocorticoids.

Adrenergic alpha-Agonists↗

PubMed1989

Renal sympathetic nerve activity and norepinephrine release in rats.

We examined relationships between changes in directly recorded renal sympathetic nerve activity (RSNA) and renal and total body spillover of norepinephrine into the bloodstream (RNEs and TBNEs, respectively) in anesthetized, adrenal-demedullated rats. Intravenous infusions of nitroprusside (NP) or phenylephrine (PH) produced reflexive, dose-dependent changes in RSNA. High-doses of NP significantly increased RSNA by 90%, RNEs by 155%, and TBNEs by 268%. High doses of PH significantly decreased RSNA by 37%, RNEs by 35%, and TBNEs by 33%. Ganglionic blockade with chlorisondamine decreased RSNA by 65% (P less than 0.05), RNEs by 10%, and TBNEs by 51% (P less than 0.05). There was a significant curvilinear relationship between mean changes in RSNA and mean changes in RNEs (r = 0.99). Simultaneous in vivo measurement of sympathetic nerve traffic and regional release of norepinephrine therefore may be useful in the assessment of presynaptic actions of drugs and hormones and in the evaluation of abnormal sympathetic neurotransmission in disease states.

Afferent Pathways↗

PubMed1988

Release of immunoreactive-neuropeptide by rat platelets.

Neuropeptide Y, a potent vasoconstrictor and cardiac depressant, is re-leased from sympathetic nerve endings. Its presence in megakaryocytes suggests this peptide might be stored in platelet granules and released during aggregation. Immunoreactive-neuropeptide Y was measured in platelet rich and platelet poor plasma, and was substantially greater in the former. Addition of collagen to platelets resulted in release of neuropeptide Y which paralleled, in a concentration-dependent manner, the degree of platelet aggregation. Adenosine diphosphate, at concentrations which induce only the first phase of aggregation and not the release reaction, caused only a minor release of neuropeptide Y. These results suggest that platelet release could be a major source of circulating neuropeptide Y and could contribute to hemodynamics of pathophysiological states involving platelet activation.

Adenosine Diphosphate↗

PubMed1988

Evidence for a direct peripheral effect of clonidine on the norepinephrine release in vivo in pithed rats.

To study the in vivo peripheral effects of clonidine on sympathetic neuronal function we measured, after different doses of clonidine, plasma norepinephrine (NE) and blood pressure (BP) responses during electric stimulation of sympathetic outflow in pithed male Sprague-Dawley rats. In this preparation, clonidine produced dose-dependent inhibition of the sympathetic stimulation-induced pressor and plasma NE responses. The dose of clonidine inhibiting the NE response by 50% (ID50) was 14.2 +/- 0.3 micrograms/kg i.v., while ID50 for the diastolic pressor response was 22.0 +/- 0.2 micrograms/kg i.v. Since clonidine did not alter the relationship between NE released into the plasma and the pressor responses, the entire effect of clonidine in decreasing the pressor response to sympathetic stimulation may be attributed to its presynaptic alpha 2-adrenoceptor-mediated inhibition of NE release.

Animals↗

PubMed1988

Role of neuropeptide Y (NPY) in cardiovascular responses to stress.

Neuropeptide Y (NPY), a putative sympathetic neurotransmitter and neuromodulator, is released during sympathetic nerve stimulation and causes vasoconstriction and cardiodepression. Whether the release of NPY contributes to stress-induced cardiovascular responses was assessed by studying i) plasma levels of circulating NPY-immunoreactivity (NPY-ir) during various stress paradigms and ii) mechanisms of action of NPY in the cardiovascular system of the rat. Plasma NPY-ir was increased by all stress situations, such as transfer to a new environment (by 52%), exposure to cold water (4 degrees C) (by 117%) and hemorrhage (4 ml/300 g body weight) (by 231%). The cold water, stress-induced, maximal increase in circulating plasma NPY-ir was delayed in relation to the peak pressor response by 10-20 min. Administration of NPY caused dose-dependent pressor responses that were greater in pithed rats--which have all centrally mediated circulatory reflexes removed--than in conscious rats. Infusion of a low pressor (8.5 +/- 1.5 mm Hg) dose of norepinephrine into conscious rats potentiated NPY-mediated pressor responses 2-fold and also tended to increase bradycardic effect of a higher dose of NPY (by 19%). Thus hypertensive and bradycardiac actions of NPY appear to depend on the level of adrenergic activity and on the interactions at the level of vascular smooth muscle, heart, and baroreceptor reflexes. During a hyperadrenergic state such as stress, cardiovascular effects of NPY may be greatly accentuated. NPY may enhance and prolong the stress-induced hypertensive responses while antagonizing adrenergic cardiostimulation.

Animals↗

PubMed1988

Differential plasma catecholamine and neuropeptide Y responses to acute stress in rats.

Neuropeptide Y (NPY) is a vasoconstrictor present in the sympatho-adrenomedullary system and may be co-released with norepinephrine (NE) and epinephrine (EPI) during sympathetic activation. We studied plasma NPY-immunoreactivity (-ir, radioimmunoassay) and catecholamine (radioenzymatic) responses during two acute stress paradigms that differ in character, intensity, and duration. The intermittent stress of footshock (0.75 and 1.5 mA, 0.5 sec duration, at 5-sec intervals, for 5 min) evoked intensity-dependent immediate increments in plasma NE and EPI, and a delayed NPY-ir response (+0.6 +/- 0.1 pmol/ml). Prolonged (60 min) immobilization caused greater increases in plasma NE and EPI levels and no changes in plasma NPY-ir until the end of the stress session (+0.3 +/- 0.1 pmol/ml). Plasma NPY-ir responses correlated with those of NE but not with EPI suggesting a sympathetic origin for the release of the peptide. Relatively greater NPY-ir responses to footshock than to immobilization may be consistent with a preferential release of the peptide by a bursting but not continuous mode of sympathetic activation. However, it may also be due to a differential activation of the sympathetic nerves and adrenal medulla by these two stress situations.

Animals↗

PubMed1987

M-chlorophenylpiperazine increases blood pressure and heart rate in pithed and conscious rats.

In pithed rats, m-chlorophenylpiperazine (m-CPP) produced marked, dose-dependent (ED50 = 0.18 mumol) increases in mean arterial blood pressure which peaked within 1 minute and were sustained over 15 minutes. Two serotonin antagonists, metergoline and ritanserin, completely blocked the pressor responses to 2.5 mg/kg m-CPP in pithed adrenal demedullated rats, while alpha-adrenergic blockade by prazosin plus yohimbine was without effect, suggesting that the doubling in blood pressure produced by m-CPP was mediated via serotonin receptors within blood vessels. Somewhat smaller increases in blood pressure over baseline values were observed after m-CPP administration to conscious, freely moving rats. A small but statistically significant increase in heart rate peaked 5 minutes after m-CPP and also was blocked by metergoline but was only minimally affected by ritanserin or the prazosin-yohimbine combination. These results with m-CPP support other evidence for two or more separable effects of serotonergic agonists on the peripheral cardiovascular system.

Adrenal Medulla↗

PubMed1987

Anterior pituitary gland modulates the release of atrial natriuretic peptides from cardiac atria.

Myocytes in the atria contain a prohormone that gives rise to atrial natriuretic peptides (ANP), which have intrinsic hemodynamic regulatory activity. Little is known about mechanisms regulating ANP release. In rats with indwelling catheters, acute blood volume expansion with 5% (wt/vol) dextrose increases the amount of circulating immunoreactive ANP by a factor of 2-3, as determined by radioimmunoassay. Pithing, which both removes neurogenic influences and interrupts humoral influences of the brain and pituitary gland on the heart, completely blocked stimulus-induced release of ANP. Because our studies using pharmacological blockade of the autonomic nervous system had suggested that neurogenic mechanisms do not play a major role in ANP release, we sought a humoral mechanism involved in ANP secretion. Basal and stimulated release of ANP were significantly blunted in hypophysectomized rats (8 days after operation) but were completely restored when the resected anterior pituitary was reimplanted under the kidney capsule. This suggests that hormones of anterior pituitary origin are required for ANP secretion in response to acute volume loading.

Adrenalectomy↗