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Biomedical subjects

C M Ferrario

Publications and source records attributed to C M Ferrario.

At least 181 records · Page 10Linked to original sources
PubMed1987

Changes in hemodynamics and myocardial contractility during chronic sodium depletion in conscious dogs.

Chronic sodium depletion has been reported to decrease ejection fraction in anesthetized dogs. We tested the hypothesis that this reduction in cardiac performance is due to either hemodynamic or humoral factors. Seven mongrel dogs were fed a low sodium diet (less than 2 mEq Na+ per day) for 5 weeks. Echocardiographic and radionuclide techniques were used to monitor cardiac function. There was a gradual but significant (p less than 0.01) decrease in ejection fraction from 61 +/- 7% (SD) at baseline to 47 +/- 8% after 5 weeks of sodium depletion in association with a fall in left ventricular end-diastolic volume. Ejection fraction did not change in five control dogs fed 55 mEq Na+ per day throughout the 5-week follow-up period. Myocardial contractility did not change in either salt-depleted or control dogs. Plasma norepinephrine levels in the coronary sinus were twice as high in salt-depleted as in control dogs, but there were no significant differences in arterial norepinephrine concentration between the two groups. Therefore, we concluded that reduced ejection fraction during sodium depletion resulted from hemodynamic changes (decreased preload). The excess available norepinephrine failed to increase myocardial contractility, suggesting a dysfunction at the cardiac adrenergic neuroeffector junction.

Animals↗
PubMed1987

Angiotensin II-induced drinking in water-deprived and nephrectomized dogs.

We evaluated the dipsogenic effects of angiotensin II (Ang II) in relation to the steady-state level of the endogenous renin-angiotensin system (RAS) by measuring water intake in 22 trained dogs during three 20 min intravenous (i.v.) infusions of [Ile5] Ang II (10, 15 and 50 ng/kg/min). Measurements obtained in normally hydrated (NHyd) dogs were compared with those obtained in dogs pretreated as follows: 24 hr water deprivation (WD); WD combined with chronic blockade of the RAS (300 mg/day X 3 days of SQ 14225) (WD + SQ); and 48 hr after bilateral nephrectomy (BNX). Both WD and WD + SQ were given water before Ang II infusion. Plasma renin activity (PRA) and serum and CSF electrolytes (cisterna magna catheter) were measured. All treatments caused a significant (p less than 0.05) increase in CSF sodium (Na+) that was not paralleled by hypernatremia in BNX dogs (142 +/- 1 vs 144 +/- 1 mEq/L in NHyd). WD and WD + SQ caused a 2- and 12-fold increase in PRA, respectively; PRA was not detectable in BNX. Suppression of blood Ang II by WD + SQ produced a reduced latency and significant enhancement of the thirst behavior elicited by Ang II at all doses; however, i.v. Ang II did not elicit drinking in the WD state. Furthermore, in BNX, the same phenomenon as in WD + SQ was observed. These data are compatible with the concept that endogenous levels of Ang II play a key role in regulating drinking behavior. However, these findings do not negate the possibility that Ang II acts synergistically with CSF Na+, but not plasma Na+, to modulate drinking behavior.

Angiotensin II↗
PubMed1987

Characterization of neurohormonal changes following the production of the benign and malignant phases of two-kidney, two-clip Goldblatt hypertension.

The neurohormonal contribution to high blood pressure was investigated in 9 conscious two-kidney, two-clip Goldblatt (2K2C) hypertensive dogs during evolution of the benign and malignant phases after application of bilateral renal clips (BRC). Serial measurements were taken of the plasma renin activity (PRA), plasma angiotensin I-immunoreactivity (Ang I-ir), plasma angiotensin II-ir (Ang II-ir), renin substrate (RS) catecholamines [epinephrine (Epi) and norepinephrine (NE)] and vasopressin (AVP). Immediately after BRC, the elevation of the blood pressure (86 +/- 3 to 110 +/- 3 mmHg, p less than 0.01) was associated with an increase in heart rate (93 +/- 3 to 114 +/- 9 beats/min, p less than 0.01). These hemodynamic changes were accompanied by increases in PRA, Ang I-ir, Ang II-ir, Epi, NE and AVP. The renin angiotensin system was activated throughout the 3 week period following BRC, as indicated by increases in PRA, Ang I-ir and Ang II-ir. Catecholamines were elevated immediately after BRC, followed by a return toward the control values. AVP underwent a slight but not significant elevation after BRC, which was sustained during the 3 weeks. Production of malignant hypertension was affected by occlusion of one of the adjustable renal clips 3 weeks after BRC. A marked elevation of the blood pressure was associated with significant increases in PRA, Ang I-ir, Ang II-ir, Epi, NE and AVP, compared with the pre-occlusion values. In addition, pharmacologic experiments were performed in 6 of 9 dogs. Administration of angiotensin I converting enzyme inhibitor (SQ 14225) reduced the blood pressure both in the benign and malignant phases of 2K2C renovascular hypertension, and a ganglionic blocking agent (hexamethonium) also decreased the blood pressure. However, a specific, vascular acting AVP antagonist failed to reduce the blood pressure significantly. From this study, it seems likely that severe renal ischemia caused by renal clipping caused the activation of the renin-angiotensin and the sympathetic nervous system and elevation of serum vasopressin. However, there are no apparent differences between the benign and malignant phases of renovascular hypertension, except for the marked elevation of neurohormone levels in malignant hypertension.

Angiotensin I↗
PubMed1987

Sodium and vasopressin modulation of renal sympathetic nerve activity.

A series of correlative studies show that sympathetic renal nerve activity (RNA) may be influenced by the concentration of sodium (Na+) in the plasma and the cerebrospinal fluid (CSF). Further study of the sites and characteristics of the interaction between Na+ and the renal nerves was undertaken in anesthetized dogs. Cerebroventricular (i.c.v.) injections of hypertonic sodium chloride (NaCl) produced a sympathetic vasoconstrictor response associated with tachycardia, increases in plasma norepinephrine and vasopressin (AVP), and a decrease in the electroneurographic activity recorded from post-ganglionic renal sympathetic nerves. Both bilateral vagotomy and intravenous administration of an AVP antagonist prevented the decrease in RNA caused by i.c.v. hypertonic NaCl, without markedly reducing the magnitude of the pressor response. The same phenomenon, however, could not be duplicated by delivery of the AVP antagonist i.c.v. In another group of dogs, the pressor activity of NaCl injected into the cisterna magna was compared before and after surgical ablation of the area postrema in the dorsal medulla. Removal of this circumventricular organ attenuated the pressor effects of NaCl given into the cisterna magna, but not those produced by i.c.v. delivery of the injectate. The data suggest that acute increases in CSF Na+ cause a differential activation of the sympathetic nervous system mediated in part by structures at or near the area postrema. At this site, circulating AVP apparently augments the inhibitory input from vagal afferents on the preganglionic renal nerve neurons.

Animals↗
PubMed1987

The distribution of substance P in the canine dorsomedial medulla.

To define the neurochemical substrates underlying cardiovascular regulatory mechanisms in the canine dorsal medulla, we characterized immunocytochemically the organization of substance P (SP) in the dorsomedial medulla. Substance P immunoreactivity was the most dense in the dorsal nucleus tractus solitarii (nTS). Varicose fibers and cells containing this neuropeptide were localized in the dorsal motor nucleus of the vagus (dmnX) and nucleus commissuralis. A few scattered fibers were observed within the area postrema. The distribution of this peptide suggests a topographical organization within the dorsomedial medulla of the dog that is closely related to the cytoarchitectural organization. In addition, the patterns of SP immunoreactivity overlap the distribution of vagal afferent fibers. These observations are discussed in relation to the possible function of SP in the dorsomedial medulla.

Animals↗
PubMed1987

Functional characteristics of neuropeptides in the dorsal medulla oblongata and vagus nerve.

The dorsomedial medulla plays an integral role in the processing of primary sensory afferent information from the respiratory, cardiovascular, and gastrointestinal systems. A correlation has also been made between the topographical organization of these vagal afferent fibers in the dorsal medulla and the distribution of a variety of neuropeptides and their receptors in this brain region. In this paper, the evidence for the presence of several neuropeptides and their receptors in the dorsomedial medulla and intra- and/or extracranial segments of the vagus nerve is presented. The possible physiological significance of these peptides and their putative receptors in the vagus nerve is also addressed, with emphasis on angiotensin II and its cardiovascular actions in this region.

Afferent Pathways↗
PubMed1987

Sodium balance and the reflex regulation of baroreceptor function.

The study of the mechanisms by which variations in salt intake affect cardiovascular function has progressed from characterizing hemodynamic and renal effects to investigating the role of sodium (Na+) on sympathetic neuronal function. The consequences of altered sodium balance on the regulation of vasomotor activity and the integration of baroreceptor reflexes is a relatively neglected area of research. This report summarizes the significance of the disturbance in baroreceptor function that is associated with alterations in Na+ homeostasis and assesses the possible mechanisms in a study of the interaction of the carotid sinus and vagal afferent reflexes in dogs exposed to sodium depletion or sodium loading. We also discuss the relationship between acute changes in cerebrospinal fluid Na+ concentration and sympathetic nerve activity in both the absence and presence of cardiopulmonary reflexes and after blockade of the systemic effects of vasopressin. The studies provide important evidence for a previously unsuspected action of Na+ upon the central circuits involved in integrating the interaction between low- and high-pressure baroreflexes.

Animals↗
PubMed1986

Basal and potassium-evoked release of angiotensin II from the rat hypothalamus.

Although the protein components of the renin-angiotensin system have been localized in the brain, it remains to be established whether or not angiotensin II (Ang II) is generated locally and secreted into the interstitial fluid of the brain. We have addressed this issue in vitro by perifusing explants of the rat hypothalamo-neurohypophysial system (HNS) (5 explants per chamber, 37 degrees C) with Krebs solution at a rate of 1 ml/min. The release of Ang II immunoreactivity (Ang II-ir) and arginine vasopressin immunoreactivity (AVP-ir) in the medium was measured 3-5 h after HNS dissection and again after addition of potassium (K+) to the perifusate. Samples of the fluid perifusing the HNS were collected for 30-min intervals and concentrated using Sep-Pak C18 cartridges. Release of Ang II-ir was significantly increased during perifusion with 70 mM K+ (from 29 +/- 14 pg/30 min to 80 +/- 17 pg/30 min, P less than 0.01). This increase coincided with a dramatic rise in the release of AVP-ir (from 50 +/- 35 pg/30 min to values above 2000 pg/30 min). The associated release of Ang II-ir in response to depolarization by K+ is consistent with the hypothesis that Ang II can be secreted by neuronal elements of the brain, possibly via a regulated pathway.

Angiotensin II↗
PubMed1986

Contribution of the vagus nerve to angiotensin II binding sites in the canine medulla.

Specific angiotensin II (Ang II) binding sites are present in the dorsal medulla of several species, and dose-related cardiovascular effects are produced by microinjection of the peptide into this region. Because the anatomical location of Ang II binding sites in the area postrema (ap), nucleus tractus solitarii (nTS), and dorsal motor nucleus of the vagus (dmnX) coincides with the topography of vagal afferent fibers and efferent motor neurons, the effect of either nodose ganglionectomy or cervical vagotomy on Ang II binding sites in the dorsomedial medulla was investigated in dogs by in vitro receptor autoradiography. Two weeks after unilateral ganglionectomy, there was a marked reduction in the density of specific Ang II binding sites in the ipsilateral ap, nTS, and dmnX, and an absence of binding sites in the region where vagal afferent fibers course through the rostral medulla. Unilateral cervical vagotomy, which has been shown to spare central processes of afferent fibers, resulted in a loss of binding only in the ipsilateral dmnX. We also show that Ang II binding sites are present in the nodose ganglion and central and peripheral processes of the vagus nerve. The data indicate that medullary Ang II binding sites are associated with both vagal afferent fibers and efferent motor neurons.

Angiotensin II↗
PubMed1986

Contribution of area postrema to pressor actions of angiotensin II in dog.

To generate quantitative data on the contribution of the area postrema (AP) to the pressor activity of angiotensin II (ANG II), the peptide (7 ng X kg-1 X min-1) was infused intravenously in 10 conscious dogs for 6 h before, and several weeks after, AP lesion. Mean arterial pressure (MAP) and heart rate (HR) were recorded continuously, and plasma renin activity (PRA), ANG II immunoreactivity (ANG II-IR), aldosterone (ALDO), arginine vasopressin (AVP), norepinephrine (NE), epinephrine (EPI), and serum Na+ and K+ were measured at 3 and 6 h. Three hours into the infusion, MAP averaged 123 +/- 2 compared with 96 +/- 2 mmHg for controls (P less than 0.01). The increases in pressure were associated with unchanged HR, but increased lability of MAP and HR. PRA fell, whereas plasma levels of ANG II-IR and ALDO rose. Plasma levels of AVP, NE, serum Na+ and K+ did not change, but plasma EPI was significantly elevated at 6 h. Removal of the AP produced mild hypotension and decreased lability. Within 8 to 21 days after AP ablation, a significant decrease in the plateau phase (3-6 h) of the ANG II pressor response was recorded in all dogs. The attenuation of the pressor effects was not sustained, since 4-7 wk after AP lesion, the increases in pressure were equivalent to those obtained during the control period. These data indicate that the AP participates in the production of the pressor response to intravenous infusion of ANG II in conscious dogs. However, in the absence of this structure, alternative mechanisms are brought into play to restore the loss of its function.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1986

Characterization of receptors for angiotensin-induced drinking and blood pressure responses in conscious rats using angiotensin analogs extended at the N-terminal.

Angiotensin II analogs with N-terminal extensions were synthesized to examine their effects on the brain and vascular angiotensin II (Ang II) receptors of the rat. Ang II, Crinia-Ang II, Thr.Ala.Gly-Ang II and Val. Ser.Leu.Thr.Ala.Gly-Ang II were all found to elicit drinking and raise blood pressure when given into the cerebrospinal fluid (CSF), and elevate blood pressure when given intravenously. When given intracerebroventricularly, the order of potency of the peptides in eliciting blood pressure and drinking responses was: Ang II (100%) = Crinia-Ang II (100%) greater than Thr.Ala.Gly-Ang II (10% blood pressure, 15% drinking) greater than Val.Ser.Leu.Thr.Ala.Gly-Ang II (5%). The order of pressor potency did not change when the Ang II analogs were given intravenously, but compared with the central effects, there was a marked difference in the relative potencies of the peptides. The potencies were: Ang II (100%) greater than Crinia-Ang II (80%) greater than Thr.Ala.Gly-Ang II (60%) greater than Val.Ser.Leu.Thr.Ala.Gly-Ang II (20%). Blood pressure and drinking responses produced by all of these peptides were markedly attenuated by the Ang II receptor antagonist, [Sar1,Thr8] Ang II. These findings indicate a difference in the Ang II receptors present in the brain and the periphery. However, no differences were noted between the central Ang II receptors mediating the pressor responses and the central Ang II receptors stimulating drinking behavior.

Angiotensins↗
PubMed1986

Cardiovascular effects of chronic naloxone infusion in normal dogs.

It has now been established that there is an interaction between the cardiovascular control systems and opiate substances. To assess the role of endogenous opiates in the long-term control of blood pressure, the opiate antagonist naloxone (0.5 mg/kg/24 h) was infused intravenously for 7 days. Chronic blockade of endogenous opiates resulted in an elevation in arterial blood pressure which averaged 11% and was sustained throughout the infusion period. This was accompanied by a significant decrease in plasma renin activity averaging -59%. These data provide support for a tonic role of opioids in the long-term control of the cardiovascular system which may involve baroreceptor function.

Animals↗
PubMed1986

Changes in central and peripheral renin-angiotensin system after furosemide injection.

To examine the effects of acute stimulation on the peripheral and central renin-angiotensin system, simultaneous sampling of blood and cerebrospinal fluid (CSF) for measurements of plasma renin activity (PRA), plasma angiotensin I-immunoreactivity (PAng I-ir), plasma angiotensin II-immunoreactivity (PAng II-ir), plasma angiotensinogen and cerebrospinal fluid angiotensin II-ir (CSF Ang II-ir) and CSF angiotensinogen was carried out following intravenous injection of furosemide (5 mg/kg) in conscious dogs. Administration of furosemide induced marked increases in PRA, Ang I-ir, PAng II-ir and CSF Ang II-ir, however, neither plasma nor CSF angiotensinogen was changed. Furthermore, a relatively large dose (20 mg/kg/min) of intravenously infused synthetic Ang II for 20 min produced a five-fold increase in PAng II-ir compared with no significant increase in CSF Ang II-ir. In spite of significant suppression of PRA and PAng I-ir, there were no significant changes in either plasma or CSF angiotensinogen. These results primarily suggest that the peripheral and the brain renin-angiotensin systems may be linked and that acute changes in the peripheral renin-angiotensin system do not alter either plasma or CSF angiotensinogen.

Angiotensin I↗
PubMed1986

Area postrema lesions augment the pressor activity of centrally administered vasopressin.

The effects of arginine vasopressin given into either the vertebral arteries, a peripheral vein (IV), or the cisterna magna of 15 morphine-chloralose anesthetized dogs were measured before and after pharmacological blockade with the antagonist [d(CH2)5 Tyr(Me) AVP]. The contribution of the area postrema to the pressor activity of vasopressin was assessed in nine other dogs by comparing the responses to vasopressin before and after surgical ablation of this structure. Administration of vasopressin either via the vertebral arteries or intravenously produced comparable gradual rises in blood pressure, accompanied by bradycardia and decreases in the plasma levels of norepinephrine. Administration of intracisternal vasopressin elicited a smaller rise in arterial pressure, tachycardia, and increases in plasma norepinephrine levels. The pressor and bradycardic effects of IV vasopressin were abolished when the antagonist was given via the same route. In contrast, intravertebral infusion of the vasopressin antagonist caused tachycardia and modest hypotension in response to intravenous or intravertebral infusions of vasopressin. Pressor effects of vasopressin given into the cisterna magna were not altered by systemic delivery of the vasopressin blocker. Removal of the area postrema selectively augmented the pressor effects of intravertebral vasopressin, whereas the pressor activity of IV vasopressin remained unchanged. These findings provide new evidence for an action of circulating vasopressin in cardiovascular regulation, mediated in part by the area postrema.

Animals↗
PubMed1986

Correlation between angiotensin II binding sites and substance P in the canine brain stem.

Specific angiotensin II (ANG II) binding sites in the dorsal aspects of the medulla oblongata of dogs and rats were shown previously to be dependent upon intact sensory and motor components of the vagus nerve. The present studies compared the distribution of ANG II binding sites in the canine medulla with the visualization of substance P immunoreactive fibres, since this peptide is known to be present in vagal afferent fibres. Dense bands of substance P-containing fibres were found to cap the tractus solitarius (TS) in the dorsal subdivision of the nucleus tractus solitarii (nTS) at a level corresponding to the region of highest ANG II binding. In addition, moderate densities of both substance P immunoreactivity and ANG II binding sites were dually localized in the medial nTS and the ventral portion of the dorsal motor nucleus of the vagus (dmnX). Since previous studies indicated that ANG II binding sites are associated with vagal afferent fibres in the nTS and efferent motor neurons in the dmnX, their apparent association with substance P immunoreactive fibres suggests that a functional interaction may occur between these two peptides in the central integration of cardiovascular function.

Angiotensin II↗
PubMed1985

Initial coronary air embolus in the differential diagnosis of coronary artery spasm.

Angiographic and electrocardiographic manifestations of initial coronary air embolism were seen in 4 patients and in a dog. All 4 patients had angina pectoris, 2 had ST elevation, 1 patient had ST depression and 1 had no electrocardiographic change after the air embolus. Although the initial diagnosis in these 4 patients was coronary artery spasm, a subsequent ergonovine test response for coronary artery spasm was negative in the 3 patients in whom it was performed. In a dog, initial injection of air in a coronary artery produced ST-segment elevation and delayed clearance of contrast material. The angiographic appearance of initial air embolus was similar in the 4 patients and in the dog. The leading edge of contrast material that followed an air embolus stopped abruptly, appeared hazy and blunt, and pulsated back and forth. The air embolus produced temporary cessation of flow in the main artery and its branches. Initial injection of air during coronary arteriography mimics coronary artery spasm by producing a syndrome characterized by angina, ischemic changes on the electrocardiogram, and delayed flow of contrast material. An initial air embolus may be differentiated from true coronary spasm by several distinctive angiographic features.

Adult↗
PubMed1985

Angiotensin II receptor localization in the canine CNS.

Specific binding of [125I]angiotensin II [(125I]Ang II) to sections of dog brain was determined by in vitro receptor autoradiography. Highly discrete, dark images representing specific binding of [125I]Ang II were observed in areas corresponding to the nucleus of the solitary tract, dorsal motor nucleus of the vagus, area postrema, ventrolateral medulla, pineal, subfornical organ, nucleus medianus, septum, organum vasculosum of the lamina terminalis and the anterior pituitary. The specific binding was frequently present either as a narrow band or tiny spot within a small portion of the nuclei to which the binding corresponded. The location of these Ang II recognition sites in regions associated with regulation of autonomic and neuroendocrine function provides further evidence for a role of this peptide within the central nervous system.

Angiotensin II↗