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Biomedical subjects

M J Brody

Publications and source records attributed to M J Brody.

At least 37 records · Page 2Linked to original sources
PubMed1991

Role of medullary lateral reticular formation in baroreflex coronary vasoconstriction.

We have recently identified a polysynaptic pathway traversing discrete regions of the hypothalamus, midbrain, and medulla, along which site-specific electrical and chemical activation produces coronary vasoconstriction as part of a sympathoexcitatory response. We tested for the potential functional significance of this pathway by examining the hypothesis that a medullary component is involved in carotid baroreflex induced coronary vasoconstriction. Coronary flow velocity was measured with a Doppler probe in anesthetized cats. Following vagotomy and propranolol, bilateral carotid occlusion produced an increase in mean arterial pressure (56 +/- 14%, means +/- S.E.M.) and in coronary vascular resistance (51 +/- 13%) which was greater than that (29 +/- 6%) expected from the concurrent rise in arterial pressure during aortic constriction. Bilateral microinjections of lidocaine into the medullary lateral reticular formation attenuated the reflex increase in pressure (11 +/- 2%) and virtually abolished the rise (8 +/- 2%) in coronary resistance. After one hour recovery, carotid occlusion again increased aortic pressure (56 +/- 13%) and coronary vascular resistance (47 +/- 15%). Microinjections of lidocaine outside this medullary region did not impair the coronary vasoconstrictor response to carotid occlusion. We conclude that the medullary lateral reticular formation contains neural elements which participate in baroreflex-induced changes in arterial pressure and coronary vascular resistance. Components of the previously described central coronary vasoconstrictor pathway may play a role in pathophysiological conditions associated with increased coronary vasomotor tone.

Animals↗
PubMed1991

Neonatal capsaicin treatment abolishes the nociceptive responses to intravenous 5-HT in the rat.

The intravenous (i.v.) administration of serotonin (5-HT) to lightly pentobarbital-anesthetized rats is known to produce a triad of reflex cardiovascular responses, distinct afferent-mediated pseudaffective reactions, and a vagally mediated inhibition of the nociceptive tail-flick (TF) reflex consistent with 5-HT acting as a noxious stimulus. In the present experiments we examined the involvement of capsaicin-sensitive afferents in mediating these responses. Lightly pentobarbital-anesthetized 16-week-old male Sprague-Dawley rats which had been treated as neonates (in the first 48 h of life) with capsaicin (50 micrograms/kg, s.c.) were compared to age-matched neonatal vehicle-treated controls. Whereas the i.v. administration of 5-HT produced a dose-dependent (6-96 micrograms/kg, i.v.) inhibition of the nociceptive TF reflex (ED50 = 48.1 +/- 11.3 micrograms/kg; n = 7) and distinct pseudaffective responses (usually by 24-48 micrograms/kg) in vehicle-treated rats, 5-HT (6-192 micrograms/kg, i.v.) failed to significantly alter TF latency or produce pseudaffective behaviors in the capsaicin-treated rats (n = 10). There was no difference in baseline TF latencies between the two groups. There were essentially no differences between vehicle- and capsaicin-treated rats with respect to the initial cardiopulmonary vagal afferent-mediated (Bezold-Jarisch reflex) decreases in heart rate and arterial blood pressure or the subsequent pressor phase. However, the magnitude of the late hypotensive phase was significantly greater in capsaicin-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Activation in the region of parabrachial nucleus elicits neurogenically mediated coronary vasoconstriction.

A role for parabrachial nucleus in cardiovascular regulation is suggested by evidence that electrical stimulation in this region elicits increase in heart rate and arterial pressure. We hypothesized that parabrachial nucleus may also be involved in control of coronary vasomotor tone. After beta-adrenergic receptor blockade in anesthetized cats, electrical stimulation in the region of parabrachial nucleus produced no change in heart rate, an increase in arterial pressure (34 +/- 6 mmHg), and a transient reduction in coronary blood flow velocity (-21 +/- 2%). Coronary resistance (72 +/- 9%) and femoral resistance (189 +/- 31%) increased markedly. The decrease in coronary blood flow velocity was abolished by stellate ganglionectomy or alpha 1-adrenergic blockade without altering pressor or femoral responses. Injection of the neurotransmitter L-glutamate or kainic acid into parabrachial nucleus also elicited coronary vasoconstriction. We conclude that electrical or chemical activation in the region of parabrachial nucleus elicits coronary vasoconstriction as part of a generalized sympathetic activation. The fact that the coronary response is elicited by chemical activation suggests that cell bodies in the region of medial parabrachial nucleus and subceruleus, as opposed to fibers of passage, are involved in this central neural coronary vasoconstriction.

Animals↗
PubMed1991

Coronary vasoconstriction during stimulation in hypothalamic defense region.

Previous studies have identified a site in lateral hypothalamus (LH) in which electrical stimulation elicits coronary vasoconstriction. We injected the retrogradely transported tracer Fast Blue to determine which brain regions project to LH. Projections to or through LH were found from the paraventricular nucleus (PVN) of the hypothalamus, bed nucleus of the stria terminalis (BNST), and dorsal raphe nucleus (DRN). In chloralose-anesthetized cats, electrical stimulation in DRN and BNST failed to increase coronary vascular resistance (CVR). However, stimulation lateral to PVN in the anterior hypothalamic area (AHA), a region not labeled by the tracer, caused a transient decrease in coronary blood flow similar to that elicited from LH. The increase in CVR was accompanied by hemodynamic changes that are characteristic of the defense reaction including a cholinergically mediated decrease in hindquarter vascular resistance. This response is likely due to activation of fibers of passage and not cell bodies, since cell bodies in the region were not retrogradely labeled and coronary vasoconstriction was not seen following microinjection of several excitatory amino acids into AHA. These data suggest that coronary vasoconstriction may be a component of the defense reaction elicited by electrical activation of AHA.

Amidines↗
PubMed1991

Vascular tone influences arterial pressure lability after sinoaortic deafferentation.

Sinoaortic deafferentation (SAD) results in increased variability of arterial pressure. The purpose of this study was to investigate the contribution of nonneurogenic, peripheral vasomotor mechanisms to this arterial pressure lability. In rats with SAD, ganglionic blockade combined with either captopril or a V1-vasopressin receptor antagonist reduced the high lability. Under these conditions, continuous infusions of phenylephrine and the endogenous vasoconstrictors angiotensin II, epinephrine, and vasopressin increased lability, suggesting that the level of vascular tone is important for maintaining lability. Hemodynamic changes in individual vascular beds did not correlate with pressure lability; however, the sum of the changes in resistance, an estimate of changes in total peripheral resistance, was significantly correlated. These results suggest that 1) direct actions of endogenous vasoconstrictors can induce marked variations of arterial pressure, presumably by sustaining a high background of vascular tone, and 2) variations in resistance of individual vascular beds do not account for the lability of arterial pressure evoked by infusion of vasoconstrictors. We conclude that vascular tone of neural and/or humoral origin is critical for the generation of fluctuations in arterial pressure associated with deafferentation of baroreceptors.

Afferent Pathways↗
PubMed1991

Role of sympathetic nerve activity in the generation of vascular nitric oxide in urethane-anesthetized rats.

The aim of the present study was to examine the involvement of the sympathetic nervous system in the generation or release of vascular nitric oxide. In urethane-anesthetized rats, the administration of the novel nitric oxide synthesis inhibitor L-N-nitro arginine (LNA) (0.02 mmol/kg i.v.) increased mean arterial pressure and renal, mesenteric, and hindquarter vascular resistances. The intravenous administration of L-arginine (60 mg/kg plus 12 mg/kg/min i.v.) produced small reductions in arterial pressure and vascular resistances and abolished the hemodynamic effects of LNA. Pretreatment with the ganglion blocking agent chlorisondamine lowered mean arterial pressure and vascular resistances, abolished the LNA-induced pressor and renal vasoconstrictor response, and attenuated the increases in mesenteric and hindquarter resistances. In contrast, the vasodilator hydralazine lowered mean arterial pressure and vascular resistances to levels equivalent to that of ganglionic blockade; however, the subsequent administration of LNA still produced significant increases in arterial pressure and regional vascular resistances. In ganglion-blocked rats in which pressure and vascular resistances were returned to normal levels by infusion of arginine vasopressin or phenylephrine, the pressor and vasoconstrictor effects of LNA were restored. However, phenylephrine was significantly more efficacious and markedly exaggerated the action of LNA. These results suggest that the sympathetic nervous system plays an important role in modulating the synthesis or release of vascular nitric oxide through the effects of 1) normal sympathetic discharge, 2) humoral activation of alpha-adrenergic receptors, and 3) vascular tone per se.

Animals↗
PubMed1991

Central nervous system and the pathogenesis of hypertension. Sites and mechanisms.

A large body of evidence indicates that the central nervous system plays an essential role in the pathogenesis of hypertension. However, in many cases the specific brain regions involved and the mechanisms by which these regions promote hypertension are not known. In recent years, research in this and other laboratories has attempted to determine the mechanisms by which neural and humoral signals arising in response to pathological conditions (often occurring in the periphery) interact with the central nervous system to produce hypertension. In this article, we illustrate the coupling of peripheral and central factors in the pathogenesis of hypertension by examining the central actions of angiotensin II and mineralocorticoids in the expression of renal hypertension and mineralocorticoid-salt hypertension, respectively. We also review recent data from this laboratory illustrating the involvement of medullary vasomotor centers in the development of neurogenic hypertension after sinoaortic deafferentation and in the maintenance of hypertension in the spontaneously hypertensive rat.

Animals↗
PubMed1991

Tonic control of arterial pressure and regional hemodynamics by supra-medullary sites.

We examined the role of pontine sites in the tonic control of vasomotor tone under normal and reduced tidal volumes. Lidocaine was microinjected in pons at the level of the Kölliker-Fuse nucleus (KFN). Injections were made bilaterally 6, 7, 8, and 9 mm below dura, and 0.9 and 2.5 mm lateral to midline. Lidocaine in KFN produced a fall (-14 mmHg) in mean arterial pressure (MAP) at normal and reduced tidal volumes. These effects were mediated primarily by a reduction in hindquarter vascular resistance. Lidocaine into a ventromedial site (8.0 mm beneath dura, 0.9 mm lateral to midline) increased MAP by increasing renal, mesenteric, and hindquarter vascular resistance. After sino-aortic deafferentation (SAD), reduced tidal volume augmented the pressor and blunted the tachycardic responses to lidocaine injected into the ventromedial pons (9.0 mm beneath dura, 0.9 mm lateral to midline). SAD also enhanced the pressor response to lidocaine injected into ventromedial pons. This work demonstrates a role for supra-medullary sites in the tonic control of vasomotor tone.

Afferent Pathways↗
PubMed1991

Cardiovascular responses produced by the systemic injection of kainic acid in conscious WKY and SH rats.

This study examined the cardiovascular effects of systemic injections of the excitatory amino acid analogue (EAA) kainic acid (KA) in conscious normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats. The injection of KA (100-1000 micrograms/kg, i.v.) produced dose-dependent but transient pressor and tachycardic responses followed by a prolonged period of bradycardia in both strains. Higher doses of KA also produced a secondary prolonged depressor response in WKY but not SH rats. Pharmacological studies demonstrated that the pressor and tachycardic responses are due mainly to increased sympathetic drive to the vasculature and heart. The KA-induced depressor response in the WKY is due principally to cardiovagal activation. After ganglionic blockade, KA produced a prolonged pressor response which was due to the release of vasopressin. These results indicate that the systemic administration of EAAs may produce their cardiovascular effects by activation of the autonomic nervous and endocrine systems and that the absence of the KA-induced hypotension in the SH rats may be related to an abnormality of cardiovagal function in this strain.

Animals↗
PubMed1991

Reduced nociceptive effects of intravenous serotonin (5-HT) in the spontaneously hypertensive rat.

This study compared the cutaneous (baseline tail-flick (TF) latencies) and visceral nociceptive responses (5-HT-induced inhibition of the TF reflex and pseudaffective responses) in lightly pentobarbital-anesthetized 16 week old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). SHR were significantly less sensitive to the nociceptive effect of i.v. 5-HT compared to WKY rats. That is, SHR had a greater quantal ED50 for inhibition of the TF reflex than WKY rats (50.0 and 15.1 micrograms/kg, respectively). SHR also showed the presence of distinct pseudaffective responses (flattening of the ears, closure of the eyes to slits and contraction of the facial musculature) at much greater doses than in WKY rats, thereby paralleling the same changes in sensitivity observed the 5-HT-induced inhibition of the TF reflex. 5-HT-induced similar cardiovascular responses in WKY and SHR except that the SHR showed a significantly greater pressor response compared to WKY rats. These results demonstrate that the SHR show a marked reduction in sensitivity to the nociceptive, but not the cardiovascular, responses to i.v. 5-HT.

Animals↗
PubMed1991

Interactions between the rostral ventral medulla and other central sites involved in vasomotor regulation.

We showed earlier that the rostral ventral medulla can be functionally and anatomically divided into the rostral ventrolateral medulla (RVLM) and the rostral ventromedial medulla (RVMM). In this study, we examined the relationship between the lateral hypothalamus and these two medullary sites. Electrical stimulation of the lateral hypothalamus produced a pressor response mediated by increases in renal and mesenteric vascular resistance. Inactivating RVLM had no effect on this response whereas inactivating RVMM significantly blunted the pressor response and the increases in renal and mesenteric resistance. In other studies, inactivating dorsomedullary sites significantly reduced arterial pressure. Unlike RVLM, these depressor responses were not significantly altered by reducing tidal volume. Inactivating sites 0.5 mm medial and lateral to the RVMM, as well as a site 0.5 mm caudal to the RVLM, resulted in depressor responses that were unaffected by reducing tidal volume. However, inactivation of a site 1.0 mm caudal to the RVLM but still within the ventrolateral medullary pressor area, resulted in a depressor response that was enhanced by reduced tidal volume. Together, these data demonstrate a functional differentiation of medullary sites controlling vasomotor outflow.

Animals↗
PubMed1990

Is there a role for an endothelium-derived relaxing factor in nociception?

Many of the circulating algesic agents released in response to ischemia produce a profound vasodilatation possibly through the release of an endothelium-derived relaxing factor (EDRF) as well as pain. We report here that intravenously administered S-nitrosocysteine, a putative EDRF, and not the nitric oxide liberating compound sodium nitroprusside produces significant alterations in nociceptive behavior that are abolished by bilateral vagotomy. These results are consistent with a role for EDRF in peripheral nociceptive mechanisms.

Analysis of Variance↗
PubMed1990

Vagal afferent-mediated inhibition of a nociceptive reflex by intravenous serotonin in the rat. I. Characterization.

The effect of intravenous (i.v.) serotonin (5-HT) on nociception and blood pressure was examined in male Sprague-Dawley rats. Intravenous 5-HT produced a dose-dependent (6-192 micrograms/kg, i.v.) inhibition of the nociceptive tail-flick (TF) reflex in lightly pentobarbital-anesthetized (ED50 = 40 micrograms/kg) and conscious rats (ED50 = 44 micrograms/kg). In the lightly pentobarbital-anesthetized rat, the blood pressure response to i.v. 5-HT was typically a triphasic response with a marked Bezold-Jarisch reflex-induced decrease in pressure (associated with a brief period of apnea) followed by a pressor phase and a subsequent delayed hypotension. In the conscious rat, the response was typically biphasic with the late hypotensive phase absent. A variety of anatomical and pharmacological manipulations were performed to characterize the 5-HT-induced inhibition of the TF reflex and associated changes in blood pressure. Prevention of 5-HT-induced reflex apnea by artificial ventilation did not affect inhibition of the TF reflex produced by 5-HT. Pharmacological manipulations were performed to mimic, as closely as possible, the acute increases and decreases in blood pressure associated with i.v. 5-HT. Nitroprusside (8 micrograms/kg, i.v.) produced a decrease in blood pressure of similar magnitude and rate as that associated with the Bezold-Jarisch reflex-induced decrease in pressure produced by 72 micrograms/kg 5-HT, but did not change TF latency from baseline. Similarly, acute increases in pressure produced by phenylephrine (8 micrograms/kg, i.v.), intended to mimic the secondary pressor effect of 5-HT, did not change TF latency. The short-acting ganglion blocker trimethaphan (5 mg/kg, i.v.) closely mimicked the late hypotensive phase produced by 5-HT, but again resulted in no change in TF latency. Pretreatment with the ganglion blocker chlorisondamine (2.5 mg/kg) abolished all depressor responses to 72 micrograms/kg 5-HT, but did not significantly affect the TF reflex. These results indicate that acute changes in blood pressure and respiration associated with i.v. 5-HT do not contribute to inhibition of the TF reflex. This conclusion was confirmed in experiments in which bilateral vagotomy abolished approximately 70% of the 5-HT-induced inhibition of the TF reflex (and all depressor responses), and resulted in a significantly greater pressor response. Finally, low thoracic spinal cord transection (T9-10) abolished the inhibition of the TF reflex produced by i.v. 5-HT. Therefore, 5-HT stimulates vagal afferents and inhibits the TF reflex by activating descending inhibitory systems from the brainstem.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1990

Connections between hypothalamus and medullary reticular formation mediate coronary vasoconstriction.

We have recently identified discrete sites within the lateral hypothalamus and medullary reticular formation that, when stimulated electrically, produce neurally mediated coronary vasoconstriction. This study examined whether these sites are part of the same coronary vasomotor pathway. The neuronal tracing dye fast blue was injected in cats into the coronary vasoconstrictor site within medullary reticular formation. Fluorescence microscopy revealed major afferent projections originating from within the same region of midbrain ventrolateral periaqueductal gray that receives projections from lateral hypothalamus. To determine the functional importance of the proposed connections between the hypothalamic and medullary sites, anesthetized cats were prepared for continuous hemodynamic measurements. Constant current electrical stimulation within lateral hypothalamus produced significant increases in heart rate (21 +/- 6%), arterial pressure (11 +/- 3%), and femoral (36 +/- 18%) and coronary resistances (14 +/- 9%) with no change in coronary flow velocity (-1.1 +/- 2.5%). After beta-adrenoreceptor blockade, significantly greater increases in arterial pressure (35 +/- 8%) and coronary resistance (39 +/- 5%) with transient decreases in coronary flow velocity (21 +/- 6%) were seen. Microinjections of lidocaine into the medullary site blocked coronary constriction produced by lateral hypothalamic stimulation (39 +/- 5% increase in coronary resistance to electrical stimulation before and 2.4 +/- 2% increase after lidocaine in medullary reticular formation). These data provide evidence that specific regions of lateral hypothalamus and medullary reticular formation are part of a common central vasomotor projection that mediates coronary vasoconstriction in addition to other hemodynamic effects.

Amidines↗
PubMed1990

Role of central mineralocorticoid binding sites in development of hypertension.

The possibility that central mineralocorticoid binding sites are involved in the development of mineralocorticoid hypertension was examined using chronic blockade of these sites with a specific mineralocorticoid receptor antagonist RU 28318 administered by intracerebroventricular (icv) infusion. The antagonist significantly attenuated the development of deoxycorticosterone acetate (DOCA)-salt hypertension, but the development of one-kidney, one-clip renal hypertension was not affected. This antihypertensive action was attributable to a central action, since intraperitoneal infusion of the same dose of mineralocorticoid antagonist did not alter the peak development of DOCA-salt hypertension. The icv infusion of RU 28318 did not change either the increase of fluid intake induced by DOCA-salt treatment or the pressor reactivity to centrally or peripherally injected arginine vasopressin and angiotensin II and peripherally administered phenylephrine. The antihypertensive action of icv infusion of the mineralocorticoid antagonist was associated with a reduction of neurogenic vasomotor tone and a restoration of impaired arterial baroreflexes. We conclude that functional integrity of central mineralocorticoid binding sites is required for the full development of DOCA-salt hypertension.

Animals↗
PubMed1990

Mechanisms of pressor response produced by stimulation of nucleus ambiguus.

We showed previously that activation of nucleus ambiguus (NA) induced bradycardia and increased arterial pressure. In this study, we compared responses produced by electrical and chemical (glutamate) stimulation of NA and adjacent rostral ventrolateral medulla (RVLM). Equivalent pressor responses were elicited from both areas. However: 1) The response from RVLM was elicited at a lower frequency. 2) Regional vascular resistance changes were different, i.e., electrical stimulation of NA increased vascular resistance in hindquarters much more than the renal and mesenteric beds. In contrast, electrical and chemical stimulation of RVLM produced a more prominent effect on the renal vascular bed. 3) Bradycardia was elicited from NA at lower current intensity. 4) Glutamate produced bradycardia only when injected into NA. Studies in rats with sinoaortic deafferentation showed that bradycardic response to activation of NA was only partly reflex in origin. We conclude that 1) NA and RVLM control sympathetic outflow to regional vascular beds differentially and 2) the NA region involves parasympathetic control of heart rate and sympathetic control of arterial pressure.

Animals↗
PubMed1990

Nociceptive afferent vagal input is enhanced after transection of the aortic depressor nerve.

To test the hypothesis that baroreceptor reflexes are involved in the reduced nociceptive responses associated with hypertension, the effects of acute intravenous doses of serotonin (0.75-144 micrograms/kg) on inhibition of the tail-flick reflex, blood pressure, and heart rate were examined in lightly pentobarbital-anesthetized Sprague-Dawley, Wistar-Kyoto, and spontaneously hypertensive rats before and after bilateral transection of the aortic depressor nerve. Before transection, the ED50s for inhibition of the tail-flick reflex in the three strains of rats were 14, 13, and 44 micrograms/kg, respectively. After bilateral transection of the aortic depressor nerve, all three strains displayed a significant increase in sensitivity toward the serotonin-induced inhibition of the tail-flick reflex (ED50s of 7, 7, and 6 micrograms/kg, respectively). There were no changes in the cardiovascular responses to serotonin after transection of the aortic depressor nerve in Wistar-Kyoto or spontaneously hypertensive rats. In Sprague-Dawley rats, however, the cardio-pulmonary cardiovascular afferent-mediated responses were enhanced. In Sprague-Dawley rats, the nociceptive sensitivity to serotonin was unaltered when administered during either the peak increase or decrease in pressure produced by intravenous phenylephrine or nitroprusside, respectively. These results suggest that 1) afferent fibers within the aortic depressor nerve provide strong tonic inhibitory influences on the noxious information conveyed by the vagus in response to intravenous serotonin and 2) these fibers appear to produce their effects by mechanisms that are unrelated to baroreceptor function.

Afferent Pathways↗