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M J Brody

Publications and source records attributed to M J Brody.

At least 73 records · Page 4Linked to original sources
PubMed1988

Effect of nucleus ambiguus lesion on the development of neurogenic hypertension.

These studies evaluated the role of the nucleus ambiguus in regulating heart rate and cardiovascular activity. Three days after lesion of the nucleus ambiguus, arterial pressure and heart rate were unchanged; however, subsequent sinoaortic deafferentation produced a significantly greater increase of pressure (156 +/- 4 vs 124 +/- 6 mm Hg) compared to sham lesion. In both groups the heart rate was increased after deafferentation and the intrinsic heart rate (rate seen after autonomic blockade with atropine and propranolol) was significantly reduced. When the sequence was reversed (deafferentation before lesion), pressure (126 +/- 6 vs 126 +/- 7 mm Hg) and heart rate (334 +/- 17 and 340 +/- 16 beats/min) were not altered; however, intrinsic rate fell more. When the nucleus ambiguus was stimulated electrically, two responses emerged: increased pressure without rate changes and increased pressure with bradycardia. These data indicate that 1) lesion of the nucleus ambiguus facilitates hypertension produced by sinoaortic deafferentation unless lesioning follows deafferentation; and 2) stimulation of the nucleus ambiguus produces a pressor effect that is independent of the bradycardic response. We conclude that the nucleus ambiguus may be related to autonomic control of both heart rate and arterial pressure.

Animals↗
PubMed1988

Tidal volume affects the response to inactivation of the rostral ventrolateral medulla.

During preliminary studies of the rostral ventrolateral medulla as a relay site for responses activated from forebrain, loss of the marked depressor effect of lidocaine, microinjected into lateral rostral ventrolateral medulla, was observed when rats were ventilated spontaneously rather than by artificial ventilation. The mechanism of this effect was studied in rats ventilated at a tidal volume of 2.5 ml. Bilateral injection of 4% lidocaine into lateral rostral ventrolateral medulla decreased mean arterial pressure by -47 +/- 8 mm Hg and heart rate by -68 +/- 21 beats/min. Reduction of tidal volume to 1.5 ml significantly attenuated the fall in mean arterial pressure and heart rate produced by lidocaine to -17 +/- 11 mm Hg and -12 +/- 8 beats/min. The decrease in tidal volume resulted in decreased arterial PO2 and pH, and increased PCO2. However, the depressor effect of lidocaine was not significantly affected by independently changing PO2 and PCO2. The physical stimuli associated with reduction of tidal volume (i.e., changes in lung inflation and chest wall movement) appeared to mediate the attenuated depressor response to the injection of lidocaine into the lateral rostral ventrolateral medulla. These data suggest that 1) tonic vasomotor activity derived from lateral rostral ventrolateral medulla is strongly influenced by altered mechanics of respiration, and 2) the anatomical location of the putative vasomotor center may not be defined by the lateral rostral ventrolateral medulla under all conditions.

Animals↗
PubMed1988

Role of the nucleus ambiguus in the regulation of heart rate and arterial pressure.

The present study examined the effect of lesion of cell bodies in the nucleus ambiguus area on the development of neurogenic hypertension and further explored the cardiovascular responses produced by chemical and electrical stimulation of the nucleus ambiguus and the neighboring C1 region. Three days after chemical lesion of the nucleus ambiguus with kainic acid, arterial pressure and heart rate were unchanged; however, subsequent sinoaortic deafferentation produced a significantly greater increase of arterial pressure (157 +/- 7 vs 132 +/- 5 mm Hg) and heart rate (436 +/- 10 vs 374 +/- 10 beats/min) compared with those produced by sham lesion. Glutamate injected into the nucleus ambiguus increased arterial pressure and heart rate at 20 nmol/100 nl and decreased heart rate at 50 nmol/100 nl. Glutamate injected into the C1 area increased arterial pressure and heart rate at both doses. Gamma-Aminobutyric acid at 50 nmol/100 nl produced bradycardia and a fall in arterial pressure when injected into both the nucleus ambiguus and C1 area. The heart rate responses to gamma-aminobutyric acid and glutamate were attenuated in sinoaortic-deafferentated rats. The nucleus ambiguus and the C1 region were mapped using electrical stimulation with microelectrodes. All points stimulated in three anteroposterior sections in the nucleus ambiguus and the C1 area produced increases in arterial pressure, whereas bradycardia was restricted to the middle of three lateral coordinates associated with the center of the nucleus ambiguus and the C1 area ventral to the nucleus ambiguus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Evidence for two functionally distinct vasomotor subregions of rostral ventral medulla.

We examined two functionally and anatomically distinct subregions of rostral ventral medulla, rostral ventrolateral medulla (RVLM, 2 mm lateral to midline) and an area we term rostral ventromedial medulla (RVMM, 1mm lateral to midline). Reducing tidal volume attenuated the depressor response to microinjection of lidocaine (200nl, 4%) into RVLM, but not into RVMM. Lidocaine reduced renal (RVR), mesenteric (MVR), and hindquarter (HQVR) vascular resistances, when injected into both sites, however HQVR was markedly reduced when RVMM was blocked. Selective stimulation with microelectrodes increased RVR, MVR, and HQVR, with RVMM producing the strongest response in HQVR and RVLM the strongest effect on RVR. Cardiovascular responses to stimulation of RVLM required the integrity of RVMM, however, the converse was not found. The integrity of RVMM, but not RVLM, was required for the cardiovascular responses produced by electrical stimulation of lateral hypothalamus. Together, these data suggest that RVLM and RVMM are both important for tonic regulation of vasomotor tone, however, these sites differ in their responses to afferent input and in the control of regional vascular resistances.

Blood Pressure↗
PubMed1988

The region of medial forebrain bundle is involved in tonic maintenance of arterial pressure and heart rate.

The role of the medial forebrain bundle (MFB) in central regulation of cardiovascular system was studied in freely moving rats. Injection of lidocaine into the ventral, but not other portions of the MFB, produced transient (approximately ten minutes) pressor and tachycardic responses. These responses resulted from an increase in sympathetic tone, since they were abolished by ganglionic blockade. The pressure response was attenuated by alpha-adrenoceptor blockade and both pressor and tachycardic responses were diminished by beta-adrenoceptor blockade. Electrolytic lesion of the same site caused long lasting pressor and tachycardic responses. Injection into the MFB of the excitatory amino acids, kainate (KA) and N-methyl-D,L-aspartate (NMDA) produced pressor and tachycardic responses accompanied by behavioral excitation, whereas no effects were produced by L-glutamate. The cardiovascular responses induced by KA and NMDA were abolished by ganglionic blockade. These results suggest that a selective region of MFB contains fibers of passage and/or cell bodies, with receptor specificity for excitatory amino acids, that are capable of influencing sympathetic sympathetic control of arterial pressure.

Amino Acids↗
PubMed1988

Central nervous system and mechanisms of hypertension.

There are several mechanisms by which the central nervous system participates in the neural and humoral alterations associated with various forms of experimental hypertension. Structures in forebrain with multiple integrative roles in neuroendocrine control of the circulation are involved. Tissue surrounding the anteroventral region of the third cerebral ventricle (AV3V region) is involved physiologically in thirst, sodium homeostasis, osmoreception, secretion of vasopressin and natriuretic factor and sympathetic discharge to blood vessels. Destruction of this tissue prevents or reverses many forms of hypertension. In genetically based spontaneous hypertension, limbic structures such as the central nucleus of the amygdala rather than the AV3V region are the necessary neuroanatomic substrate. Recent evidence suggests that a circumventricular organ in brain stem, the area postrema, is also involved in the mediation of several forms of experimental hypertension. In renin- and nonrenin-dependent forms of renal hypertension, two major factors activate central mechanisms. First, direct central actions of angiotensin, acting through receptors in the subfornical organ and organum vasculosum of the lamina terminalis, increase sympathetic discharge and secretion of vasopressin through mechanisms integrated at the level of the AV3V region. Second, sensory systems originating in the kidney can activate increased sympathetic discharge through complex projection pathways involving forebrain systems. Mineralocorticoid hypertension appears to involve enhanced secretion of vasopressin and central vasopressinergic mechanisms also dependent on the AV3V region. Reciprocal connections between key central areas involved in control of arterial pressure provide the neuroanatomical basis for central nervous system participation in hypertension.

Blood Pressure↗
PubMed1987

Dissociation of antinociceptive from cardiovascular effects of stimulation in the lateral reticular nucleus in the rat.

The lateral reticular nucleus (LRN) in the caudal ventrolateral medulla has been implicated in the regulation of spinal nociceptive transmission and hemodynamics. Experiments were undertaken to examine the relationship between inhibition of the tail flick reflex and cardiovascular effects produced by electrical stimulation in the LRN in rats lightly anesthetized with pentobarbital. Intensity- and frequency-dependent increases in mean arterial pressure and vascular resistance in the hindquarter, mesenteric, renal and caudal arterial beds were observed. Inhibition of the tail flick reflex, however, occurred at intensities of electrical stimulation which produced no significant changes in mean arterial pressure or vascular resistance in any of the arterial beds studied. Selective stimulation of cell bodies in the LRN by microinjection of glutamate similarly inhibited the tail flick reflex but produced significant reductions in mean arterial pressure, without substantially affecting regional vascular resistances. These results suggest that the antinociceptive and depressor effects of stimulation in the LRN are mediated by activation of cell bodies, while pressor effects produced by focal electrical stimulation are mediated by activation of fibers of passage. The descending inhibition produced by stimulation in the LRN is independent of stimulation-produced cardiovascular responses.

Animals↗
PubMed1987

Central and peripheral mechanisms of arterial pressure lability following baroreceptor denervation.

Deafferentation of sinoaortic baroreceptors produces a marked increase in the lability of arterial pressure that is sustained chronically. Studies reviewed in this paper were designed to determine the mechanisms responsible for generating arterial pressure lability. Pharmacological interruption of the humoral vasopressin and angiotensin systems failed to alter arterial pressure lability. In contrast, blockade of sympathetic nervous system transmission at both ganglionic and alpha-adrenergic receptor levels significantly attenuated lability. A similar effect was observed with the peripheral neurotoxin, 6-hydroxydopamine. After blockade of sympathetic transmission, a further reduction in lability was produced by blocking the renin-angiotensin or vasopressin systems. The dissociation of the level of arterial pressure from lability was achieved with parachloroamphetamine which raised arterial pressure but reduced lability. A substantial peripheral contribution to lability was obtained in experiments in which the alpha-adrenergic agonist, phenylephrine, produced a marked increase in lability in both normal and baroreceptor-denervated animals in which humoral and neural transmission were blocked. These data demonstrate that following baroreceptor deafferentation, arterial pressure lability is produced primarily by the sympathetic nervous system and secondarily by circulating humoral factors that appear to act on vascular smooth muscle to induce fluctuations in the level of arterial pressure.

Afferent Pathways↗
PubMed1987

Electrical stimulation in perifornical lateral hypothalamus decreases coronary blood flow in cats.

Based on evidence implicating the central nervous system in the regulation of coronary vascular resistance and the knowledge that the hypothalamus is a central site for integration of cardiovascular control, studies were undertaken to determine if electrical stimulation in the hypothalamus produced coronary vasoconstriction. In anesthetized cats, following beta-adrenergic receptor blockade, stimulation in perifornical lateral hypothalamus produced a transient decrease in coronary blood flow velocity (30 +/- 5%), a small pressor effect (7 +/- 2 mmHg), and an initial decrease in hindquarter blood flow velocity (51 +/- 5%). The decrease in coronary flow velocity, which had an onset latency of 1-3 s and a duration of 5-15 s, was abolished by ipsilateral stellate ganglionectomy and by intravenous and intracoronary prazosin. The coronary vasoconstriction produced by hypothalamic stimulation was not different from that produced by cardioaccelerator nerve stimulation. These results suggest that electrical stimulation of a hypothalamic site produces an alpha-adrenergic receptor-mediated decrease in coronary blood flow that is unmasked by beta-adrenergic receptor blockade, requires the integrity of ipsilateral cardiac sympathetic innervation, and mimics the coronary response to cardioaccelerator nerve stimulation.

Adrenergic beta-Antagonists↗
PubMed1987

Regulation of arterial pressure lability in rats with chronic sinoaortic deafferentation.

After chronic (2-6 wk) sinoaortic deafferentation (SAD), rats exhibit slight increases in mean arterial pressure (MAP) and heart rate and marked increases in arterial pressure lability. Neither antagonists of humoral vasoconstrictors angiotensin and vasopressin nor acute hypophysectomy altered MAP or lability after chronic SAD. Ganglionic blockade produced hypotension and significantly reduced lability in SAD rats but decreased MAP and increased lability in normal rats. Although chlorisondamine reduced lability in rats with SAD to levels observed in similarly treated sham-operated rats, lability was significantly greater in both groups than in saline-treated sham-operated rats. When intact or SAD rats were administered chlorisondamine plus either captopril or a vasopressin antagonist, pressure lability was returned to levels seen in intact untreated animals. Selective antagonism of alpha 1- or alpha 2-adrenergic receptors did not markedly alter lability in SAD rats. Combined alpha-adrenergic blockade reduced lability in SAD rats and increased lability in intact rats, similar to chlorisondamine treatment. These data suggest that chronic SAD establishes arterial pressure variability that is maintained or generated in large part by the sympathetic nervous system through mechanisms dependent on higher central structures or descending efferent sympathetic nerves. The data further suggest that peripheral mechanisms may also be involved in arterial pressure regulation in baroreceptor-deficient rats.

Animals↗
PubMed1987

Role for the median preoptic nucleus in centrally evoked pressor responses.

Recent evidence suggests an important role for the median preoptic nucleus (MnPO) in cardiovascular responses evoked by angiotension II (ANG II). We therefore planned to determine whether selective inactivation of this nucleus would produce deficits in pressor responsiveness to centrally administered ANG II and carbachol. Chronic disruption of MnPO by electrolytic lesion produced pressor deficits to centrally administered ANG II and carbachol but did not change resting arterial pressure. In addition, blockade of neuronal activity in MnPO produced by the microinjection of the local anesthetic lidocaine reversibly attenuated pressor responses to these agents without producing any change in resting arterial pressure. The microinjection of ANG II itself into sites in which lidocaine blocked ANG II pressor responses had no effect on arterial pressure but did produce drinking. These data suggest that the MnPO, although not acting as a receptor site for the pressor effect of ANG II, plays an important role in mediating the pressor response evoked by centrally administered ANG II and carbachol.

Angiotensin II↗
PubMed1987

Vasoconstrictor and vasodilator sites within anteroventral third ventricle region.

Previous studies have shown that electrical stimulation of the rat anteroventral third ventricle (AV3V) region produces a characteristic pattern of hemodynamic effects, i.e., renal and mesenteric vasoconstriction, and hindquarters vasodilation. In the present study, we localized the vasoconstrictor and vasodilator effects to specific subregions of the AV3V. In urethan-anesthetized rats prepared with arterial catheters and pulsed Doppler flow probes, we assessed the effects of electrical stimulation of four nuclei within AV3V on mean arterial pressure and renal, mesenteric, and hindquarters resistance. These nuclei were the organum vasculosum lamina terminalis (OVLT), ventral nucleus medianus (median preoptic nucleus), anterior (precommissural) nucleus medianus (median preoptic nucleus), and periventricular preoptic nuclei. Stimulation was carried out by use of a tungsten microelectrode. Stimulation of the OVLT consistently provoked stimulus-locked increases in arterial pressure coupled with increases in mesenteric and renal vascular resistance. Ganglionic blockade with chlorisondamine prevented these responses, demonstrating that they were mediated neurogenically. Stimulation of the three remaining nuclei produced decreases in arterial pressure, hindquarters vasodilation, and little change in mesenteric and renal vascular resistance. No changes in heart rate were observed with stimulation of any of the four nuclei. These results suggest that the vasoconstrictor and pressor functions of the AV3V region are localized in or near the OVLT region, whereas the remaining nuclei of the AV3V region mediate vasodilator and depressor responses.

Animals↗
PubMed1987

Functional identification of the central projections of afferent renal nerves.

The central integration of cardiovascular reflexes produced by activation of renal sensory mechanisms was examined by studying arterial pressure and regional blood flow responses to electrical stimulation of the renal afferent nerves. Spinal transection, rostral to the entry into the cord of renal afferent projections, abolished the cardiovascular response consisting of an a fall in arterial pressure, mesenteric vasoconstriction and vasodilation in the hindquarters. Several supraspinal structures at medullary, midbrain and forebrain levels were identified by lesion studies to be important for the reflex responses. Lesion of NTS abolished the hindquarter vasodilator response but left the mesenteric vasoconstrictor response intact. Lesions of the parabrachial complex produce similar effects whereas lesions in the periventricular preoptic region of hypothalamus abolished mesenteric vasoconstriction and left hindquarter vasodilation unaffected. These studies demonstrate that cardiovascular reflexes elicited by activation of renal sensory nerves require integrity of spinal pathways and are differentially integrated at several levels of the neuraxis.

Afferent Pathways↗
PubMed1987

Neurogenic regulation of coronary blood flow: evidence for a central nervous system pathway.

The central representation of neurogenically mediated coronary vasoconstriction produced by activation of the sympathetic nervous system was examined in anesthetized cats instrumented for continuous recording of coronary and femoral blood flows, arterial pressure, and heart rate. Electrical stimulation in a small region of perifornical lateral hypothalamus increased arterial pressure, heart rate, and coronary blood flow; following the administration of propranolol, a transient coronary vasoconstrictor response was unmasked. The response was mediated over the sympathetic nervous system since it was blocked by stellate ganglionectomy and by the alpha 1-adrenergic receptor antagonist prazosin. Projections to and from the lateral hypothalamic site were identified by using anterograde and retrograde pathway-tracing techniques. Paraventricular nucleus projected to lateral hypothalamus, which in turn made connections in periaqueductal gray with projections terminating in lateral reticular formation of medulla. Coronary vasoconstrictor responses qualitatively identical to those produced by hypothalamic stimulation were found with activation of paraventricular nucleus and lateral reticular formation. Interruption of neuronal transmission in the medullary site blocked the response produced by activation of hypothalamic site. These data demonstrate that coronary vasoconstriction mediated over the sympathetic nervous system can be elicited from an interconnected pathway that links sympathoexcitatory sites in forebrain and brainstem.

Animals↗
PubMed1987

Hemodynamic pharmacology of p-chloroamphetamine, a serotonin agonist, in conscious rats.

The hemodynamic effects of p-chloroamphetamine (PCA), an indirect serotonin (5-HT) agonist, were studied in conscious, unrestrained rats. PCA caused an immediate hypotension and bradycardia followed by a dose-dependent increase in mean arterial pressure (MAP), which lasted for 15 to 60 min, associated with variable effects on heart rate. An intermediate dose increased MAP and resistance in hindquarter and mesenteric, but not renal, vascular beds. The pressor effect of PCA was blocked by prazosin and by 6-hydroxydopamine plus adrenal demedullation, but not by 6-hydroxydopamine or adrenal demedullation separately. Ganglionic blockade with chlorisondamine or beta adrenoceptor blockade with propranolol potentiated the pressor response to PCA, whereas several manipulations of central 5-HT systems (fluoxetine, methysergide and 5,7-dihydroxytryptamine) reduced but did not eliminate the hypertension observed after PCA. The initial bradycardia and hypotension were abolished by chlorisondamine or atropine but not reduced by any other pretreatment, whereas the variable heart rate response was converted to a marked, sustained tachycardia by ganglionic blockade or atropine and to a consistent bradycardia by propranolol and peripheral sympathectomy. The data suggest that PCA causes an immediate central or reflex vagal activation to decrease heart rate and MAP, followed by a central 5-HT-mediated increase in sympathetic activity that increases MAP. Most of the pressor effect observed between 5 and 30 min after PCA appears to be mediated by a direct effect on release of norepinephrine and epinephrine from sympathetic nerve terminals and the adrenal medulla, respectively. Only a minor part of the hemodynamic response to PCA appears to be attributable to its effect on release of 5-HT in the brain.

Adrenal Medulla↗
PubMed1986

A comparison of the hemodynamic effects produced by electrical stimulation of subnuclei of the paraventricular nucleus.

The paraventricular nucleus of the hypothalamus (PVN) is composed of magnocellular and parvocellular subdivisions. Magnocellular neurosecretory neurons project to the neurohypophysis while parvocellular neurons send monosynaptic axonal projections to autonomic regulatory areas in the brainstem and spinal cord. In the present study, we investigated the hemodynamic effects produced by selective magnocellular or parvocellular stimulation. In urethane anesthetized rats with intact baroreflexes, magnocellular and parvocellular stimulation produced only slight differences in hemodynamic responses, however, following acute sinoaortic denervation a clear difference was observed. Parvocellular stimulation produced an increase in arterial pressure and vasoconstriction in gut, kidney and skeletal muscle. Magnocellular stimulation produced little effect on arterial pressure and marked vasodilation in the hindquarters. Blockade of peripheral vasopressin vascular receptors did not affect the vasoconstrictor response produced by stimulation of PVN. These data are consistent with the hypothesis that the long descending neural projections of the parvocellular PVN subserve a selective vasoconstrictor function.

Animals↗