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Biomedical subjects

H D Schultz

Publications and source records attributed to H D Schultz.

At least 37 records · Page 2Linked to original sources
PubMed1995

Vagal neuroeffector mechanisms affecting transpulmonary pressure in the intact rat.

Experiments were conducted with chloralose-urethan anesthetized rats to assess the effects of 1) bilateral stimulation of the cervical vagus nerves and 2) parasympathomimetic and sympathomimetic agents. Transpulmonary pressure (Ptp) was used as an index of airway smooth muscle tone, and peak inspiratory Ptp (Ptppeak) values were used for a comparison of responses. In untreated animals, vagal stimulation elicited an increase in Ptppeak of 155%. Cooling of the vagus nerves to 15 degrees C abolished the response of Ptppeak to vagal stimulation. Although isoproterenol (1-10 micrograms/kg i.v.) did not alter resting Ptppeak, it did prevent vagal stimulation from evoking an increase in Ptppeak. Nadolol (1.5 mg/kg i.v.) augmented the increase in Ptppeak elicited by vagal stimulation. Vagal stimulation did not evoke any change in Ptppeak after the administration of both nadolol and atropine or after combined administration of nadolol, atropine, and either serotonin aerosol or prostaglandin F2 alpha. In rats pretreated with capsaicin 1 wk before the experiment, vagal stimulation evoked an increase in Ptppeak that was not statistically different from that of untreated control animals. Therefore, nonadrenergic noncholinergic systems did not appear to play an independent role in the response of the airways to the activation of the vagus nerves.

Administration, Inhalation↗
PubMed1995

Neuropeptide depletion impairs postischemic recovery of the isolated rat heart: role of substance P.

OBJECTIVES: Ischemia of the myocardium stimulates cardiac sensory nerve endings resulting in the local release of neuropeptides. The significance of the release of neuropeptides, such as substance P (SP), for the function of the heart during ischemia and reperfusion is not known. We examined the effects of both chronic and acute neuropeptide depletion and of SP administration on contractile function and rhythmicity of the isolated rat heart during global ischemia and subsequent reperfusion. METHODS: Experiments were conducted on the isolated perfused heart from vehicle and capsaicin-pretreated rats (100 mg/kg) to deplete neuropeptides from peripheral nerve terminals. The hearts were perfused with Krebs-Henseleit solution (95%O2 + 5% CO2, 37 degrees C, at constant pressure of 90 cmH2O). Left ventricular developed and diastolic pressures (LVDevP and LVEDP), heart rate (HR) and coronary flow (CF) were measured. Hearts were subjected to 20 min global no-flow ischemia and 30 min reperfusion. RESULTS: Prior to interrupting coronary flow, LV pressures, HR and CF did not differ between vehicle and capsaicin-pretreated rats. However, throughout the reperfusion period, the recovery of LVDevP, HR and CF in hearts from capsaicin-pretreated rats was consistently less than in control hearts (P < 0.05), and the incidence of fibrillation during reperfusion was higher (P < 0.05). In other experiments, acute perfusion of isolated hearts with capsaicin (10(-6) M) for 5 min before ischemia had a similar limiting effect during reperfusion. Administration of SP (10(-6)-10(-9) M) to capsaicin-pretreated hearts before ischemia restored their ability to recover contractile function and CF during reperfusion. Administration of SP to untreated hearts before ischemia also improved their recovery above normal during reperfusion and decreased the incidence of fibrillation without affecting postischemic CF. The beneficial effects of SP were abolished by an NK-1 receptor antagonist, CP-96,345 (10(-6) M). CONCLUSIONS: These data indicate that sensory neuropeptides play a role in protection of the isolated heart against ischemic damage and suggest a role of SP in the resistance of the myocardium to ischemia and reperfusion injury.

Animals↗
PubMed1994

Activation of cardiac vagal afferents by oxygen-derived free radicals in rats.

Myocardial ischemia and reperfusion can evoke excitation of cardiac vagal afferent nerve endings and activation of a cardiogenic depressor reflex (Bezold-Jarisch effect). We postulate that oxygen-derived free radicals, which are well known to be produced during prolonged ischemia and reperfusion, contribute to this excitation. Hydroxyl radicals derived from hydrogen peroxide (H2O2) activate abdominal sympathetic afferents and produce reflex excitation of the cardiovascular system. However, it is not known whether inhibitory vagal cardiac afferents are activated by oxygen-derived free radicals. We recorded activity from 52 single vagal afferent fibers in 29 rats; the endings of these fibers were located in the walls of all four chambers of the heart. Thirty-three (63%) of these fibers were classified as chemosensitive C-fiber endings because of their irregular discharge under resting conditions, their activation in response to the topical application of capsaicin (1 to 10 micrograms) to the surface of the heart encompassing the receptive field, and their conduction velocities. Fourteen (27%) of the remaining fibers were found to be mechanoreceptors. Topical application of H2O2 to the heart activated 50% of the chemosensitive endings and did not directly affect cardiac mechanoreceptors. Activity increased by 498% at a dose of 3 mumol (P < .001). This effect was reproducible and dose dependent and was not due to [H+]. Topical application of xanthine/xanthine oxidase (20 mmol/0.03 mU) activated 8 of the 12 chemosensitive fibers tested and had no direct effect on mechanosensitive fibers. Activity increased by 287% (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1994

Activation of cardiac vagal afferents in ischemia and reperfusion. Prostaglandins versus oxygen-derived free radicals.

Myocardial ischemia and reperfusion can evoke excitation of cardiac vagal nerve endings and activation of a cardiogenic depressor reflex (Bezold-Jarisch effect). We postulate that oxygen-derived free radicals, which are known to be produced during prolonged ischemia and reperfusion, contribute to this afferent excitation. We recorded activity from 47 chemosensitive vagal afferent fibers in 31 rats; the endings of these fibers were located in the left ventricle. Chemosensitive endings were identified with topical applications of capsaicin (10 micrograms) to the surface of the heart. Reactivity of the endings to oxygen-derived free radicals was assessed by topical application of H2O2 (3 to 9 mumol). Activity of the vagal fibers was recorded during 30 minutes of occlusion of the left anterior descending coronary artery (LAD) and 10 minutes of subsequent reperfusion. The activity of chemosensitive endings within the ischemic zone increased in the first 2 minutes of LAD occlusion from 2.2 +/- 0.4 to 4.3 +/- 0.9 impulses per second (107 +/- 30% increase, P < .05). This increased activity waned after 3 to 5 minutes of occlusion. Endings outside the ischemic zone did not increase, their activity at the beginning of ischemia. Reperfusion caused a rapid elevation of activity only in chemosensitive fibers whose endings were found to respond to topical H2O2. The reperfusion-sensitive endings were located both within and outside the ischemic zone of the left ventricle. Indomethacin (5 mg/kg i.v., 20 minutes before occlusion) effectively prevented activation of chemosensitive afferent endings at the beginning of LAD occlusion regardless of their sensitivity to H2O2 but had no effect on the activation at reperfusion.

Afferent Pathways↗
PubMed1991

Arachidonic acid metabolites regulate the secretion of atrial natriuretic peptide in cultured rat atrial cardiocytes.

Prostaglandins F2 alpha and E2 increase release of immunoreactive (irANP) in primary cultures of rat atrial cardiocytes. This effect is independent of cell density in the cultures and does not appear to operate through a cAMP-dependent mechanism. Studies that probed the PGF2 alpha effect with a number of different pharmacological antagonists suggest that it is tied to a calmodulin-dependent step. This latter effect does not appear to be related to increased calcium entry through voltage-gated channels in the plasma membrane nor to mobilization of ryanodine-sensitive intracellular calcium pools. Inhibitors of the lipoxygenase pathway, a second avenue of arachidonate metabolism, resulted in a decrease in irANP release from cultured atrial or ventricular cardiocytes. Leukotriene C4, a lipoxygenase product, had a modest effect to promote irANP release over a 24-h period. However, pretreatment of anesthetized rats with nordihydroguarietic acid, a lipoxygenase inhibitor, had no effect on stretch-dependent release of irANP from the heart in vivo. These findings suggest that the prostaglandins represent the more important group of arachidonate metabolites in regulating irANP release physiologically.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Interactions between ANP and ANG II in regulating blood pressure and sympathetic outflow.

In anesthetized rats with sinoaortic denervation, intracerebroventricular (icv) injection of atrial natriuretic peptide (ANP) resulted in decreased mean arterial blood pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) (depressor effects), whereas icv angiotensin II (ANG II) produced increases in these variables (pressor effects). The depressor effects of ANP were slower in onset and longer in duration than the pressor effects of ANG II. Intracerebroventricular injection of the ANG II-receptor blocker sarthran or the ANG II-synthesis inhibitor captopril resulted in a significant reduction in MAP; HR and RSNA were not affected. Both sarthran and captopril abolished the depressor responses to icv ANP. In contrast, injection of an anti-rat ANP antibody, which blocked the depressor effects of icv ANP, did not by itself modify MAP, HR, or RSNA, nor did the antibody affect the pressor responses to icv ANG II. These data suggest that, in this animal model, the depressor effects of icv ANP are mediated by the inhibition of brain ANG II-dependent neural activity. These results also demonstrate that, in this preparation, the endogenous ANG II system actively contributes to the maintenance of basal MAP, whereas the central ANP system, at least in regions accessible to the antirat ANP antibody, plays little role in this maintenance.

Angiotensin II↗
PubMed1991

Cigarette smoke in lungs evokes reflex increase in tracheal submucosal gland secretion in dogs.

Stimulation of pulmonary C-fibers (PCs) by capsaicin and of rapidly adapting receptors (RARs) by reduced lung compliance reflexly increases airway submucosal gland secretion in dogs. Because both PCs and RARs are stimulated by cigarette smoke (nicotine being the primary stimulus), we performed experiments in anesthetized open-chest artificially ventilated dogs (with aortic nerves cut) to determine whether cigarette smoke reflexly stimulates airway secretion. We measured submucosal gland secretion by counting the hillocks in a 1.2-cm2 field of tracheal epithelium coated with tantalum dust. Secretion was stimulated by delivery of 40-320 ml smoke from high-nicotine cigarettes to the lower trachea, secretion rate increasing from 7.4 +/- 1.3 to 48.1 +/- 5.1 hillocks.cm-2.min-1. Results of cutting the pulmonary vagal branches or carotid sinus nerves or both indicated that the secretory response was initiated by stimulation of lower respiratory vagal afferents and augmented several seconds later by stimulation of carotid chemoreceptors. Results of cooling the cervical vagus nerves to 7 and 0 degrees C indicated that most of the vagally mediated increase in secretion was due to stimulation of afferent lung C-fibers.

Animals↗
PubMed1990

Cyclooxygenase blockade attenuates responses of group IV muscle afferents to static contraction.

Cyclooxygenase products of arachidonic acid might be some of the substances that accumulate in contracting muscle to cause the reflex increases in arterial pressure and ventilation that are evoked by exercise. Recently, cyclooxygenase blockade has been shown to attenuate the reflex cardiovascular responses to static muscular contraction in anesthetized cats. Group IV afferents are believed to comprise part of the afferent arm of the reflex arc, the activation by which static muscular contraction causes these cardiovascular effects. We therefore examined the effects of indomethacin and aspirin, two cyclooxygenase-blocking agents, on the responses to static contraction of group IV afferents with endings in the triceps surae muscles of anesthetized cats. We found that indomethacin (5 mg/kg iv) decreased the responses to contraction of each of eight group IV afferents tested. Likewise, aspirin (50 mg/kg iv) decreased the responses to contraction of each of four group IV afferents tested. On the other hand, we found that arachidonic acid (2 mg) injected into the femoral artery did not increase the responses to contraction of four group IV afferents that were stimulated by this maneuver. In addition, arachidonic acid injection did not cause any of seven group IV afferents not stimulated by static contraction to become responsive to this maneuver. Nevertheless, arachidonic acid injection with the muscle at rest stimulated five of seven contraction-insensitive and two of four contraction-sensitive group IV afferents. Our data suggest that cyclooxygenase metabolites of arachidonic acid are needed for the full expression of the responses of group IV muscle afferents to static contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Central administration of atrial peptide decreases sympathetic outflow in rats.

Previously, we reported that intravenous (iv) administration of atrial natriuretic peptide (ANP) evokes a decrease in sympathetic outflow. This effect requires an afferent input from vagal C-fibers. Here, we examined the effect of intracerebroventricular (icv) administration of ANP on sympathetic outflow, as well as the potential role of central mechanisms in mediating the sympathoinhibitory effects evoked by systemic administration of the peptide. In anesthetized rats with arterial baroreceptors intact, injection of ANP (100-500 ng) into the third ventricle did not affect renal and least-splanchnic sympathetic nerve activities, heart rate, and mean arterial pressure. After sinoaortic denervation, however, icv injection of ANP (100 ng) decreased these variables by 8 +/- 1 and 9 +/- 2% of control nerve activity, 9 +/- 3 beats/min, and 13 +/- 2 mmHg, respectively (P less than 0.05). The inhibitory sympathetic and cardiovascular effects of icv ANP were dose dependent, with responses seen after doses too small to produce systemic effects (less than 100 ng). Vagal blockade did not abolish the effects evoked by icv ANP. In addition, iv administration of ANP did not alter reflex responses to graded electrical stimulation of afferent vagal C-fibers. Furthermore, central administration of an antiserum directed against rat ANP did not alter the inhibitory sympathetic responses evoked by iv administration of the peptide. Taken together, these results indicate that centrally administered ANP, like systemic ANP, decreases sympathetic outflow, heart rate, and blood pressure; however, the central and peripheral actions of the peptide can be distinguished and appear to be independent.

Animals↗
PubMed1990

Sensitization of group III muscle afferents to static contraction by arachidonic acid.

The afferent arm of the reflex are responsible for the pressor response to static contraction is comprised of group III and IV fibers. The nature of the contraction-induced stimulus activating these fibers remains unclear. Evidence suggests that most group III afferents are sensitive to mechanical stimuli, whereas most group IV afferents are sensitive to metabolic stimuli. Recently, in anesthetized cats, stimulation of group III mechanoreceptors has been shown to have a role in the reflex pressor response to static contraction. In skin, the sensitivity of thin fiber mechanoreceptors to distortion of their receptive fields has been shown to be increased by both cyclooxygenase and lipoxygenase products of arachidonic acid metabolism. Therefore, in barbiturate-anesthetized cats we recorded the responses of group III muscle afferents to static contraction before and after arachidonic acid (1-2 mg ia) and/or indomethacin (5 mg/kg iv). Arachidonic acid increased the responses of group III afferents (n = 11) to contraction by 265% (from 0.17 +/- 0.07 to 0.62 +/- 0.24 impulses/s; P less than 0.025). Indomethacin decreased the responses of group III afferents (n = 9) to contraction by 61% (from 1.00 +/- 0.37 to 0.39 +/- 0.16 impulses/s; P less than 0.025). Arachidonic acid given after indomethacin increased the responses of two of four group III afferents to contraction. We conclude that both cyclooxygenase and lipoxygenase products of arachidonic acid metabolism sensitize group III muscle afferents to static contraction.

Action Potentials↗
PubMed1990

Prostaglandins regulate the synthesis and secretion of the atrial natriuretic peptide.

We have examined the effects of several PGs on the synthesis and release of the atrial natriuretic peptide (ANP) in vivo and in vitro. PGF2 alpha infusion in anesthetized rats resulted in a significant increase in plasma immunoreactive (ir) ANP levels in vivo despite effecting only modest changes in hemodynamics. The PGs were also effective at promoting irANP secretion in primary cultures of neonatal rat atrial and ventricular cardiocytes. PGF2 alpha increased irANP release with half-maximal induction seen at approximately 10(-8) M; PGE2 was somewhat less effective and prostacyclin (PGI2) was without effect. The PGs also increased ANP mRNA levels in these cells, suggesting that these agents exert a major effect on the synthesis as well as the secretion of the prohormone. Transient expression analysis of atrial cells transfected with 2,500 bp of human (h) ANP 5' flanking sequence linked to a chloramphenicol acetyltransferase (CAT) reporter demonstrated that PGF2 alpha (10(-5) M) increased hANP promoter activity approximately twofold relative to the control. PGF2 alpha had no effect on the promoterless control (pSV0-lamin CAT). Treatment of cultured atriocytes with high concentrations of a cyclooxygenase inhibitor resulted in a significant suppression of ANP secretion in vitro and a truncation of the plasma ANP response to volume infusion in vivo. Taken together these studies support a role for PGs as regulators of cardiac ANP synthesis and secretion, and suggest an additional mechanism whereby eicosanoids may act to control cardiovascular and renal homeostasis.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1989

Pulmonary rapidly adapting receptors reflexly increase airway secretion in dogs.

We attempted to determine whether stimulation of pulmonary rapidly adapting receptors (RARs) increase tracheal submucosal gland secretion in anesthetized open-chest dogs. Electroneurographic studies of pulmonary afferents established that RARs but not lung C-fibers were stimulated by intermittent lung collapse during deflation, collapse being produced by removing positive end-expiratory pressure (PEEP, 4 cmH2O) or by applying negative end-expiratory pressure (NEEP, -4 cmH2O). We measured tracheal secretion by the "hillocks" method. Removing PEEP or applying NEEP for 1 min increased secretion from a base line of 6.0 +/- 1.1 to 11.8 +/- 1.7 and 22.0 +/- 2.8 hillocks.cm-2.min-1, respectively (P less than 0.005). After PEEP was restored, dynamic lung compliance (Cdyn) was 37% below control, and secretion remained elevated (P less than 0.05). A decrease in Cdyn stimulates RARs but not other pulmonary afferents. Hyperinflation, which restored Cdyn and RAR activity to control, returned secretion rate to base line. Secretory responses to lung collapse were abolished by vagal cooling (6 degrees C), by pulmonary vagal section, or by atropine. We conclude that RAR stimulation reflexly increases airway secretion. We cannot exclude the possibility that reduced input from slowly adapting stretch receptors contributed to the secretory response.

Afferent Pathways↗
PubMed1988

Vagal C-fiber blockade abolishes sympathetic inhibition by atrial natriuretic factor.

Administration of atrial natriuretic factor (ANF) to anesthetized rats decreases renal nerve activity (RNA), an effect prevented by vagotomy but not by atropine. We sought to determine whether afferent vagal C-fibers mediate the inhibition of sympathetic outflow. ANF (2.5 micrograms/kg iv) decreased mean arterial pressure (MAP) by 25 +/- 2 mmHg, RNA by 11 +/- 5%, and least splanchnic nerve activity (LSNA) by 10 +/- 4% in anesthetized rats with arterial baroreceptors intact, and by 40 +/- 3 mmHg, 28 +/- 7%, and 23 +/- 4%, respectively, in sinoaortic-denervated rats. Inhibition of RNA and LSNA by ANF was reduced slightly by cooling the vagi to 6 or 7 degrees C, a temperature at which conduction in A-fibers was blocked and that in C-fibers attenuated; inhibition was abolished when C-fibers were blocked by cooling to 0 degrees C. We conclude that the inhibition of RNA and LSNA by ANF was mediated by afferent vagal C-fibers. We also obtained evidence that the aortic nerves contribute to ANF-induced inhibition of RNA. Our results support the notion that ANF evokes a generalized decrease in sympathetic tone that contributes to the hypotension, cardiac inhibition, and natriuresis accompanying systemic administration of the peptide.

Animals↗
PubMed1987

Characteristics of C fibre baroreceptors in the carotid sinus of dogs.

1. We compared the pressure-response characteristics of C fibre and A fibre baroreceptors in the carotid sinus of anaesthetized dogs, recording impulses from the sinus nerve and varying mean pressure in the vascularly isolated sinus, which was distended with a pulsatile pressure. Functional stimulus-response curves were obtained by gradually increasing sinus pressure above and decreasing it below a set-point of 100 mmHg. Baroreceptors were identified by a pulsatile discharge synchronous with the pulsations in sinus pressure. A and C fibre baroreceptors were identified by the conduction velocities and blocking temperatures of their axons. 2. The pressure-response characteristics of C and A fibre baroreceptors differed in several respects. C fibres had a pulsatile firing threshold 50 mmHg higher than that of A fibres (105.8 +/- 1.8 and 54.6 +/- 2.9 mmHg, respectively), an average maximal sensitivity 35% of that of A fibres (0.39 and 1.12 impulses s-1 mmHg-1, respectively), and a maximal frequency (at 220 mmHg) 29% of that of A fibres (24.5 and 84.3 impulses/s, respectively). Although invariably pulsatile at pressures above threshold, the firing pattern of C fibre baroreceptors tended to be more irregular than that of their A fibre counterparts. 3. Impulses were also recorded from C fibres that were stimulated by increasing sinus pressure but had an irregular, non-pulsatile discharge, a high pressure threshold (averaging 154.1 +/- 7.2 mmHg), and a low maximum frequency (10.8 +/- 2.4 impulses/s). 4. Cooling the sinus nerve progressively attenuated conduction in both A and C fibres, A fibres being blocked between 12 and 4 degrees C (mean 6.8 degrees C) and C fibres between 4 and -1.5 degrees C (mean 1.0 degree C). Although cooling the sinus nerve to 7 degrees C did not block conduction in all A fibres, impulse activity in baroreceptor A fibres at a carotid sinus pressure of 200 mmHg was no greater than that at a pressure of 75 mmHg. By contrast, at 7 degrees C baroreceptor C fibres still provided a signal proportional to sinus pressure. 5. Our results suggest that A and C fibre baroreceptors subserve different reflex functions, the former signalling changes in arterial pressure both above and below the normal set-point, the latter only changes above. They also suggest that differential cold blockade may be a useful tool to determine the contribution of C fibre baroreceptors to cardiovascular reflexes.

Action Potentials↗
PubMed1987

Carotid sinus baroreceptors modulate tracheal smooth muscle tension in dogs.

Arterial baroreceptors are known to influence airway smooth muscle tone. Thus, increasing carotid sinus pressure from 20 to 200 mm Hg causes reflex tracheal dilation. However, the effects of changing sinus pressure around a normal arterial pressure set-point of 100 mm Hg have not been examined. In anesthetized, artificially ventilated dogs, we distended the vascularly isolated carotid sinuses with a pulsatile pressure and recorded isometric tension in an upper tracheal segment. The aortic nerves were cut. Increasing mean carotid sinus pressure in steps between 100 and 200 mm Hg decreased tracheal tension, heart rate, and arterial blood pressure; decreasing sinus pressure between 100 and 25 mm Hg had the opposite effect. Changing carotid sinus pressure still evoked tracheal responses when systemic arterial pressure was held constant. Increasing and decreasing carotid sinus pulse pressure around a constant mean pressure evoked similar changes in tracheal tension. All reflex effects were abolished by cutting or cooling (0 degree C) the carotid sinus nerves; tracheal responses were abolished by the carotid baroreflex were of comparable magnitude to those triggered by stimulating pulmonary stretch receptors, laryngeal receptors, and pulmonary C-fibers. Our results indicate that carotid sinus baroreceptors exert a tonic influence on the upper airways by a vagal cholinergic pathway, increasing and decreasing tracheal smooth muscle tension as blood pressure varies around the normal set-point.

Afferent Pathways↗