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Biomedical subjects

M B Patel

Publications and source records attributed to M B Patel.

At least 19 recordsLinked to original sources
PubMed2006

Dynamics of tissue ubiquitin pools and ubiquitin-proteasome pathway component activities during the systemic response to traumatic shock.

Based on the biological significance of the ubiquitin-proteasome pathway (UPP) and its potential role during sepsis, burns and ischemia-reperfusion injury, we hypothesized that the systemic response to traumatic shock (TS) is accompanied by tissue-specific UPP alterations. Therefore, we studied tissue ubiquitin pools, chymotryptic- and tryptic-like proteasome peptidase activities and ubiquitin-protein ligation (UbPL) rates in skeletal muscle, heart, lung, liver, spleen and kidney using a clinically relevant porcine model (bilateral femur fracture/hemorrhage followed by fluid resuscitation). TS induced a systemic reduction of tissue-specific high molecular mass ubiquitin-protein conjugates (>50 kDa). Free ubiquitin was unaffected. The dynamic organ patterns of ubiquitin pools paralleled the typical physiological response to TS and resuscitation. Reduction of ubiquitin-protein conjugates was most pronounced in heart and lung (p<0.05 vs. control) and accompanied by significant increases in proteasome peptidase and UbPL activities in these organs. Unlike all other tissues, spleen proteasome peptidase and UbPL activities were significantly reduced 10 h after TS. These findings support the concept that the UPP could play an important role in regulation of cell functions during the early whole-body response to TS. The UPP might be a therapeutic target to improve the metabolic care after TS, particularly in the heart, lung, and spleen.

Animals↗
PubMed2006

Distribution and interrelationship of ubiquitin proteasome pathway component activities and ubiquitin pools in various porcine tissues.

The ubiquitin-proteasome pathway fulfills major biological functions, but its physiologic tissue distribution and the interrelationship between pathway component activities and ubiquitin pools are unknown. Therefore, we analyzed free and conjugated ubiquitin, ubiquitin-protein ligation rates (UbPL) and chymotryptic- and tryptic-like proteasome peptidase activities in porcine skeletal muscle, heart, lung, liver, spleen and kidney (n=5 each). There were considerable differences between tissues (p<0.05 for all parameters). Lung and spleen showed high levels of free and conjugated ubiquitin and high UbPL. Proteasome activities were highest in kidney and heart. There were linear relationships between tryptic-like and chymotryptic-like proteasome peptidase activities (r(2) = 0.624, p<0.001) and between free and conjugated ubiquitin tissue levels (r(2) = 0.623, p<0.001). Tissue levels of free and conjugated ubiquitin correlated linear with UbPL (p<0.005), but they were not correlated with proteasome peptidase activities. The results suggest that tissue ubiquitin pools are tightly regulated and indicate a constant proportion of conjugated ubiquitin. They further support the hypothesis that ubiquitin-protein ligase systems, and probably deubiquitylating enzymes, are key regulators of ubiquitin homeostasis. The detected differences are suggestive of tissue-specific roles of ubiquitin-proteasome pathway components. Besides the known importance of the ubiquitin proteasome pathway in heart, kidney and the immune system, the results suggest the lung as another organ in which ubiquitin proteasome pathway components may also significantly contribute to disease processes.

Animals↗
PubMed2006

Regulation of the ubiquitin proteasome system in mechanically injured human skeletal muscle.

Metabolic consequences of direct muscle trauma are insufficiently defined. Their effects on the ubiquitin-proteasome pathway (UPP) of protein degradation in human skeletal muscles are as yet unknown. Thus, we investigated whether the UPP is involved in the metabolic response evoked in directly traumatized human skeletal muscles. Biopsies were obtained from contused muscles after fractures and from normal muscles during elective implant removal (control). As estimated by western blot analyses, concentrations of free ubiquitin and ubiquitin protein conjugates were similar in extracts from injured and uninjured muscles. Ubiquitin protein ligation rates were reduced after injury (1.5+/-0.2 vs. 1.0+/-0.15 fkat/microg; p=0.04). Chymotryptic-, tryptic- and caspase-like proteasome peptidase activities (total activity minus activity in the presence of proteasome inhibitors) increased significantly after trauma (p=0.04 - 0.001). Significant increases in total chymotryptic- and caspase-like activities were attributable to proteasome activation. Our results extend the possible role of the UPP in muscle wasting to direct muscle trauma. They further suggest that the effects of direct mechanical trauma are not limited to the proteasome and imply that ubiquitin protein ligase systems are also involved. Based on the potential role of the UPP in systemic diseases, it might also be a therapeutic target to influence muscle loss in critically ill blunt trauma patients, in which large proportions of muscle are exposed to direct trauma.

Adolescent↗
PubMed2001

Determination and use of a transition state for the enzyme estrone sulfatase (ES) from a proposed reaction mechanism.

Using the postulated mechanism for the enzyme estrone sulfatase (ES), we have determined a possible transition state for the reaction catalysed by ES as a representation of the active site. Using the derived structure, we have undertaken the molecular modelling of several steroidal and non-steroidal inhibitors in an attempt to rationalise the inhibitory activity of a number of potent inhibitors.

Catalytic Domain↗
PubMed2001

Conditioned blood reperfusion during angioplasty (CoBRA) treatment of acute myocardial infarction.

Acute myocardial infarct (MI) results in ischemia distal to lesions which puts heart muscle at risk for reperfusion injury (RI). Neutrophils, platelets and complement are putative mediators of RI. Recent advances in filtration technology provide integrated neutrophil and platelet removal together with complement-attenuating properties in a single blood-conditioning device. The present study characterizes the properties of a blood-conditioning filter and describes its clinical effect when used in conjunction with active hemoperfusion for acute MI. The filter reduces leukocytes by 99.9998 +/- 0.0002% (p<0.0001) and platelets by 99.9934 +/- 0.0069% (p<0.0001). Human plasma, derived from heparinized blood that was 'conditioned' by filtration, was studied using the Langendorff isolated rabbit heart preparation. The deposition of membrane attack complex and the resultant functional myocardial impairments [reflected in hemodynamic and biochemical measurements, including developed pressure, coronary blood flow, lymph-derived myocardial creatine kinase (CK)] are significantly attenuated by blood conditioning. Integration of the blood-conditioning filter into an active hemoperfusion system during primary percutaneous transluminal coronary angioplasty (PTCA) for acute MI (n=8) did not delay the procedure or cause any complications. Reperfusion of occluded coronary arteries with 300 cm3 of conditioned blood led to significant improvement in echocardiographic global wall motion scores (in standard deviations) following treatment (-1.64 +/- 0.18 to -1.45 +/- 0.15, p=0.02). Initial reperfusion of totally occluded coronary arteries with conditioned blood leads to acutely improved ventricular function. Collectively, these data provide a strong indication for continued investigation of conditioned blood reperfusion in angioplasty following acute MI for the long-term effect upon recovery of salvagable myocardium.

Adult↗
PubMed2000

Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in low density lipoprotein receptor-deficient mice.

The role of macrophage lipoprotein lipase (LPL) expression in atherosclerotic lesion formation was examined in low density lipoprotein receptor (LDLR(-/-)) mice using dietary conditions designed to induce either fatty streak lesions or complex atherosclerotic lesions. First, LDLR(-/-) mice chimeric for macrophage LPL expression were created by transplantation of lethally irradiated female LDLR(-/-) mice with LPL(-/-) (n = 12) or LPL(+/+) (n = 14) fetal liver cells as a source of hematopoietic cells. To induce fatty streak lesions, these mice were fed a Western diet for 8 weeks, resulting in severe hypercholesterolemia. There were no differences in plasma post-heparin LPL activity, serum lipid levels, or lipoprotein distribution between these two groups. The mean lesion area in the proximal aorta in LPL(-/-) --> LDLR(-/-) mice was significantly reduced by 33% compared with LPL(+/+) --> LDLR(-/-) mice, and a similar reduction (38%) in lesion area was found by en face analysis of the aortae. To induce complex atherosclerotic lesions, female LDLR(-/-) mice were lethally irradiated, transplanted with LPL(-/-) (n = 14), LPL(+/-) (n = 13), or LPL(+/+) (n = 14) fetal liver cells, and fed the Western diet for 19 weeks. Serum cholesterol and triglyceride levels did not differ between the three groups. After 19 weeks of diet, the lesions in the proximal aorta were complex with relatively few macrophages expressing LPL protein and mRNA in LPL(+/+) --> LDLR(-/-) mice. Analysis of cross-sections of the proximal aorta demonstrated no differences in the extent of lesion area between the groups, whereas en face analysis of the aortae revealed a dose-dependent effect of macrophage LPL on mean aortic lesion area in LPL(-/-) --> LDLR(-/-), LPL(-/+) --> LDLR(-/-), and LPL(+/+) --> LDLR(-/-) mice (1.8 +/- 0. 2%, 3.5 +/- 0.5% and 5.9 +/- 0.8%, respectively). Taken together, these data indicate that macrophage LPL expression in the artery wall promotes atherogenesis during foam cell lesion formation, but this impact may be limited to macrophage-rich lesions.

Animals↗
PubMed2000

Human cytomegalovirus UL37 immediate-early regulatory proteins traffic through the secretory apparatus and to mitochondria.

The human cytomegalovirus (HCMV) UL36-38 immediate-early (IE) locus encodes the UL37 exon 1 (pUL37x1) and UL37 (gpUL37) regulatory proteins, which have anti-apoptotic activities. pUL37x1 shares its entire sequence, including a hydrophobic leader and an acidic domain, with the exception of one residue, with the amino terminus of gpUL37. gpUL37 has, in addition, unique N-linked glycosylation, transmembrane and cytosolic domains. A rabbit polyvalent antiserum was generated against residues 27-40 in the shared amino-terminal domain and a mouse polyvalent antiserum was generated against the full-length protein to study trafficking of individual UL37 proteins in human cells that transiently expressed gpUL37 or pUL37x1. Co-localization studies by confocal laser scanning microscopy detected trafficking of gpUL37 and pUL37x1 from the endoplasmic reticulum to the Golgi apparatus in permissive U373 cells and in human diploid fibroblasts (HFF). Trafficking of gpUL37 to the cellular plasma membrane was detected in unfixed HFF cells. FLAG-tagged gpUL37 trafficked similarly through the secretory apparatus to the plasma membrane. By using confocal microscopy and immunoblotting of fractionated cells, gpUL37 and pUL37x1 were found to co-localize with mitochondria in human cells. This unconventional dual trafficking pattern through the secretory apparatus and to mitochondria is novel for herpesvirus IE regulatory proteins.

Animals↗
PubMed1996

Patient misunderstanding of dosing instructions.

OBJECTIVE: To compare outpatients' understanding of medication dosing instructions written in terms of daily frequency with patients' understanding of instructions specifying hourly intervals. DESIGN: Prospective cohort study involving patient interviews. SETTING: A university hospital outpatient pharmacy. PATIENTS: Five hundred patients presenting new and refill prescriptions to the hospital outpatient pharmacy. INTERVENTION: Patients were interviewed using a standardised questionnaire. MEASUREMENTS AND MAIN RESULTS: Of the 71 patients with prescriptions specifying dosing instructions in hourly intervals (e.g., q6h), 55 (77%) misinterpreted the recommended frequency of dosage compared with only 4 (0.99%) of the 429 patients with dosing instructions specifying daily frequency (e.g., qid) (relative risk 83; 95% confidence interval 31-200). This difference remained when patient subgroups were evaluated by education level, new versus refill prescriptions, and analgesic versus nonanalgesic medications. CONCLUSIONS: This study indicates that the intended dosing regimen is frequently misunderstood when the physician writes outpatient prescriptions in hourly intervals. To promote optimal patient compliance, the outpatient prescription label should state the number of times a day a medication is to be taken.

Adult↗
PubMed1996

Gross, histological, and microvascular anatomy and biomechanical testing of the spring ligament complex.

In recent years there has been an increased interest in the treatment of acquired pes planus. The breakdown of the medial longitudinal arch is most often seen at the talonaviculocalcaneal articulation. This suggests a relationship between the ligamentous complex at this articulation and acquired pes planus. This study was undertaken to gain a better understanding of the gross, histologic, and microvascular anatomy, as well as the biomechanics of the ligamentous structures surrounding the talonaviculocalcaneal articulation. Cadaver dissections of 38 fresh-frozen feet were performed. Detailed descriptions of the gross anatomy of the superomedial calcaneonavicular ligament, inferior calcaneonavicular ligament, and the superficial deltoid ligament were recorded. Their relationships to the posterior tibialis tendon and to the bones of the talonaviculocalcaneal articulation are described. The histology and microvascularity of these structures were also studied. Preliminary biomechanical testing was performed. It was found there are two definitive anatomic structures that are commonly called the spring ligament: the superomedial calcaneonavicular ligament (SMCN) and the inferior calcaneonavicular ligament (ICN). The SMCN ligament was found to have histologic properties that suggest significant load bearing. The histology of the ICN ligament suggests a pure tensile load function. The deltoid ligament and the posterior tibialis tendon had direct attachments to the SMCN ligament in all specimens. An articular facet composed of fibrocartilage was found in each SMCN ligament specimen. The microvascular structures showed an avascular articular facet present in the ligament. The biomechanical testing showed that the SMCN ligament and ICN ligament had strength similar to ankle ligaments. This study suggests this "spring ligament complex" has more of a "sling" function for the talar head. It is hoped that the better understanding of this region will add to our understanding of the etiology of pes planus and possible treatment alternatives.

Biomechanical Phenomena↗
PubMed1994

The superior peroneal retinaculum: an anatomic study.

The superior peroneal retinaculum is thought to be the primary restraint to subluxation and/or dislocation of the peroneal tendons as they pass posterior to the distal fibula. The descriptions in anatomy texts vary widely. This anatomical study describes the different patterns of insertions for the superior peroneal retinaculum and its relationship to the peroneal tendons and the ligaments of the lateral ankle.

Ankle Joint↗
PubMed1993

Desquamative interstitial pneumonia: a case presentation.

A 25-year-old African-American woman presented in the emergency room of a community hospital complaining of shortness of breath. The patient was admitted with a diagnosis of atypical pneumonia. Her respiration worsened despite intravenous erythromycin, nebulized albuterol, 40% oxygen via ventimask, and guaifenesin. An open lung biopsy revealed pulmonary tissue showing interstitial fibrosis with lymphocytes and histiocytes scattered within the fibrous tissue. Numerous alveoli contained mononuclear cells as seen in desquamative interstitial pneumonia. The patient did not respond to methylprednisolone and died on the eighteenth hospital day.

Adult↗
PubMed1992

Chronic elevation of norepinephrine in conscious dogs produces hypertrophy with no loss of LV reserve.

Elevated plasma catecholamine levels may cause both myocardial hypertrophy and tissue damage. To determine whether the left ventricle from dogs with chronic norepinephrine infusion can sustain additional functional loads, we altered ventricular preload or afterload and determined both global and left ventricular (LV) wall function. Dogs were instrumented to measure LV wall function, LV internal base diameter, and LV pressures and were allowed to fully recover. Preload was altered by volume loading and afterload by injection of phenylephrine. Osmotic infusion pumps were implanted to continuously release norepinephrine at 0.5 micrograms.kg-1.min-1 for 28 days, and the volume loading and phenylephrine were repeated on days 14 and 28. Heart rate decreased, whereas there were no differences in mean arterial pressure, maximum first derivative of LV pressure (dP/dt), LV dP/dt/developed pressure of 40 mmHg, LV dP/dt/end-diastolic circumference, slope of the pressure-diameter relation, peak systolic wall stress, LV/end-diastolic diameter, or LV/end-systolic diameter during norepinephrine infusion. Diastolic and systolic wall thickness and chamber weights were increased (P less than 0.05). Indexes of diastolic function, including end-diastolic pressure, end-diastolic pressure-end-diastolic diameter relationship, maximum negative dP/dt, and the time constant (tau) were unchanged after chronic norepinephrine infusion, although maximum end-diastolic pressure during volume loading was increased from 17.7 +/- 2.0 to 21.7 +/- 1.0 mmHg. Chronic norepinephrine infusion did not alter tau, and tau increased equivalently with phenylephrine injection in both normal (36 +/- 1 to 62 +/- 5 ms) dogs and in those chronically infused with norepinephrine (36 +/- 1 to 56 +/- 5 ms).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Altered pressure-volume relation of right atrium and venoatrial junction in diabetic rats.

Previous studies have indicated a blunted volume reflex in diabetic rats. This alteration of the volume reflex may be due to differences in distensibility of the right atrium and venoatrial junction, which contain a large number of volume receptors. This study was designed to determine whether the distensibility of the right atrium and venoatrial junction is altered in the diabetic rat. The distensibility was assessed by measuring the stiffness constants [slope of pressure-volume (P-V) curve] of the right atrium and venoatrial junction in 2-wk streptozotocin-induced diabetic rats. The P-V data of the right atrium and venoatrial junction were measured in control and diabetic rats over a range of 0-10 mmHg by infusion of isotonic saline in KCl-arrested, in situ hearts. Similar P-V data also were determined in an additional group of diabetic rats under daily insulin treatment, which normalized plasma glucose. The mean slope of the P-V curve of the right atrium and venoatrial junction in the diabetic rats was significantly greater than the mean slope of the control and insulin-treated diabetic rats. The results indicate that diabetic rats have stiffer right atria and venoatrial junctions, which may reduce stimulation of the volume receptors to acute volume loading. In addition, the increased stiffness in the diabetic rats was prevented by chronic insulin treatment. An altered afferent limb of the volume reflex in diabetic rats contributing to blunted diuretic and natriuretic responses to volume loading may be due to these documented changes in the distensibility of the right atrium and venoatrial junction.

Animals↗
PubMed1991

Renal responses to acute volume expansion and atrial natriuretic factor in streptozotocin-induced diabetic rats.

The purpose of this study was to determine whether diuretic and natriuretic effects are altered in response to volume expansion (VE) and atrial natriuretic factor (ANF) in 4-week diabetic rats. Diabetes was induced in two groups of male Sprague Dawley rats using streptozotocin (STZ), while a control group of rats was treated with vehicle alone, four weeks prior to the experiment. One group of diabetic rats was treated daily with insulin for the four weeks prior to the experiment. Before, during and after VE (1.2 ml/min for 15 min), urine flow and sodium excretion were measured from innervated and denervated kidneys in the three groups of anesthetized rats. Then the renal response to infusion of ANF (0.25 microgram/kg/min for 15 min) were observed in these rats. During VE, urine flow and sodium excretion from innervated kidneys, but not from denervated kidneys, were significantly lower in diabetic rats than those in control rats. Urine flow and sodium excretion from innervated as well as denervated kidneys of the diabetic rats failed to increase compared to the control rats in response to ANF. Correcting the diabetic condition with insulin (third group) rectified the blood glucose levels and the blunted responses to either VE or ANF. At the initial level, glomerular filtration rate (GFR) was not significantly different among the three groups. During VE and ANF infusion, changes in GFR was not parallel to changes in excretory parameters, therefore the hemodynamic change may not be the main reason for the blunted renal responses in diabetic rats. This study demonstrates that: (1) the volume reflex is blunted in the 4-week diabetic rats, which is in part due to the presence of tonic renal nerve activity, (2) renal responses to ANF are blunted in the 4-week diabetic rats, and (3) insulin treatment in diabetic rats normalizes the altered renal responses to either acute volume expansion or ANF.

Analysis of Variance↗
PubMed1991

Atrial compliance determines the nature of passive atrial stretch and plasma atrial natriuretic factor in the conscious dog.

STUDY OBJECTIVE: The aim was to measure changes in atrial wall function over a wide range of atrial filling pressures in order to determine the relationship governing the atrial stretch in vivo. DESIGN: Acute graded haemorrhage, 30 ml.kg-1, was used to reduce atrial stretch, and volume loading with 1000 ml saline was used to increase atrial stretch. EXPERIMENTAL MATERIAL: Awake mongrel dogs (n = 6) were instrumented for the measurement of left atrial appendage pressure and diameter; awake mongrel dogs (n = 4) were instrumented for measurement of left and right atrial appendage pressures and diameters. MEASUREMENTS AND MAIN RESULTS: During haemorrhage, left atrial pressure and diameter decreased progressively, and plasma atrial natriuretic factor fell from 44 (SEM 10) to 25(5) pg.ml-1 (p less than 0.05). Calculated left atrial wall stress and minute wall stress fell by 80(5.8)% and 72(15)% (p less than 0.05 from control). During volume expansion, however, atrial wall stress and minute wall stress markedly increased and plasma atrial natriuretic factor increased by more than 500%. The relationship between left atrial pressure and diameter was a typical exponential compliance curve during volume loading and haemorrhage for atrial systole, the A wave, and for atrial diastole, the V wave. During volume expansion right atrial pressure and diameter were also related exponentially. Left atrial passive stretch, as measured by V wave wall stress, increased more than right atrial stretch during volume loading. Changes in atrial filling in conscious dogs therefore result in typical exponential changes in atrial pressure and diameter in both atria. Plasma atrial natriuretic factor only increased at high filling pressures. The relationship between passive V wave minute wall stress and plasma atrial natriuretic factor also fitted an exponential curve. Thus when atrial filling was reduced, plasma atrial natriuretic factor fell by only 50% from control, while when atrial filling increased over the physiological range (up to 15 mm Hg left atrial pressure), it rose only to 100 pg.ml-1. CONCLUSIONS: Very high atrial appendage wall stresses are required to increase plasma atrial natriuretic factor markedly. Atrial stretch and the release of atrial natriuretic factor are non-linearly related. The stimulus for atrial natriuretic factor release is related to the exponential changes in atrial function due to the underlying atrial compliance relationship.

Animals↗
PubMed1991

Altered function and structure of the heart in dogs with chronic elevation in plasma norepinephrine.

BACKGROUND: We have previously shown that chronic elevation of plasma norepinephrine leads to a functional independent increase in left ventricular weight. The goals of the present study were to determine quantitatively the component of the myocardium that accounted for the observed structural changes and to determine the function of the hypertrophied myocardium. METHODS AND RESULTS: Mongrel dogs were chronically instrumented for measurement of arterial and left ventricular pressures, left ventricular internal diameter, and left ventricular wall thickness. Subcutaneous osmotic pumps were implanted to release norepinephrine continuously for 28 days. Hemodynamics were measured with dogs in the quietly resting state and during infusions of isoproterenol at 0.1 and 0.5 micrograms/kg/min before and on days 14 and 28 during the infusion of norepinephrine. The hemodynamic response to 10 micrograms/kg phenylephrine, given as a bolus, was also assessed before norepinephrine and 28 days during the infusion of norepinephrine, and the end-systolic pressure-diameter or wall-stress-diameter relations were calculated. On day 28, hearts were arrested in diastole and perfusion fixed in situ. Tissue samples were prepared for electron microscopy and morphometry. Hemodynamic studies showed that isoproterenol (0.5 micrograms/kg/min) reduced mean arterial pressure (MAP) to the same point on each experimental day, and the increases in indexes of contractility were reduced during norepinephrine infusion. Left ventricular dP/dtmax increased 131 +/- 24% on control day, only 67 +/- 20% on day 14, and 55 +/- 18% on day 28. Similar changes were observed in dP/dt/DP40 and dP/dt/end-diastolic circumference. However, Emax, the slope of the end-systolic pressure-diameter or wall stress diameter relations, was unchanged, suggesting that inotropic state was not altered. Morphometric studies showed that the cross-sectional area of myocytes increased by 55%, but myocyte and capillary densities decreased by 34% and 29%, respectively (p less than 0.05) in dogs with high norepinephrine levels. There were no differences in volume fractions of myocytes, capillary lumen, or interstitium or capillary-to-myocyte ratio. CONCLUSIONS: The myocardium of dogs with high norepinephrine levels shows reduced inotropic response to beta-adrenergic stimulation despite the increases in left ventricular mass and left ventricular wall thickness, which are a result of growth of the cardiac myocytes and characteristic of concentric hypertrophy. These data suggest that chronic adrenergic stimulation of the heart reduces the beta-receptor coupling to the contractile response without importantly compromising left ventricular function.

Animals↗
PubMed1991

Carotid baroreceptor function in dogs with chronic norepinephrine infusion.

Carotid baroreceptor function, the compliance of the carotid sinus wall, and the structure of the carotid artery were examined in dogs with elevated plasma norepinephrine (2,000-4,000 pg/ml) for 28 days. The dogs with high norepinephrine were normotensive (100 +/- 4.0 versus 98 +/- 4.0 mm Hg; p greater than 0.05) with bradycardia (65 +/- 4.0 versus 87 +/- 16 beats/min; p less than 0.05) compared with normal dogs in the conscious state. However, after pentobarbital anesthesia blood pressure was significantly higher in dogs with chronic norepinephrine infusion (165 +/- 6 mm Hg) compared with normal dogs (132 +/- 6 mm Hg). To assess baroreceptor sensitivity, multiunit carotid baroreceptor activity was recorded from the right carotid sinus nerve, and the carotid sinus wall compliance (sonomicrometers) was measured during nitroglycerin and phenylephrine injections. The threshold and saturation pressures increased from 96 +/- 3.9 to 117 +/- 4.2 mm Hg and from 145 +/- 4.3 to 171 +/- 5.7 mm Hg, respectively, in the normal dogs compared with the high norepinephrine dogs. The most striking differences were the marked increases in sensitivity of carotid baroreceptors (0.47 +/- 0.05 versus 1.99 +/- 0.45 spikes.sec-1.mm Hg-1; p less than 0.01) and maximum firing frequency of the baroreceptors (24 +/- 3.1 versus 48 +/- 4.4 spikes/sec; p less than 0.01), whereas the carotid sinus wall compliance was unchanged (0.014 +/- 0.003 versus 0.012 +/- 0.002 mm/mm Hg; p greater than 0.05). Similar alterations were observed using single fiber recordings, that is, an increase in threshold and saturation pressures and slope of baroreceptor units in dogs with elevated norepinephrine. The wall thickness and area of the carotid artery were determined. Both increased significantly (0.77 +/- 0.06 versus 1.30 +/- 0.12 mm and 9.0 +/- 0.8 versus 11.9 +/- 0.9 mm2; p less than 0.05) in dogs chronically infused with norepinephrine while the dry weight-to-wet weight ratio of left carotid artery tissue also increased from 26.0 +/- 0.73% to 29.0 +/- 0.57%. These studies indicate that 1) one of the possible mechanisms responsible for bradycardia in the conscious dogs with high norepinephrine is enhanced sensitivity of carotid baroreceptors; 2) the enhanced sensitivity of carotid baroreceptors is not due to a change in compliance of the carotid sinus wall; and 3) chronic elevation of norepinephrine causes hypertrophy or hyperplasia of the wall of the common carotid artery.

Animals↗