Biomedical subjects

D D Lund

Publications and source records attributed to D D Lund.

At least 37 records · Page 2Linked to original sources

PubMed1991

Presynaptic regulation of cardiac sympathetic function in hypoxic guinea pigs.

In the normal heart, presynaptic cholinergic muscarinic and alpha 2-adrenergic mechanisms modify the fractional rate constant for norepinephrine (NE) synthesis (kNE), an index of sympathetic neural function. To evaluate presynaptic regulation of kNE, conscious guinea pigs subjected to normoxia and then hypoxia (n = 7-8 in each group) were pretreated with 1) vehicle; 2) a cholinergic muscarinic antagonist, methyl atropine; 3) an alpha 2-antagonist, yohimbine; or 4) a combination of the two. An increase of kNE was determined from incorporation of radiolabeled tyrosine into NE in a control period (arterial PO2 130 +/- 1.7 Torr, PCO2 36 +/- 0.5 Torr) and during a hypoxic state (PO2 49.6 +/- 1.0 Torr, PCO2 36 +/- 0.5 Torr). Hypoxia activated kNE in the atrioventricular node and right ventricular moderator band in vehicle-treated animals (P less than 0.05). Sympathetic activation was more general, however, because alpha 2-presynaptic influence acted to limit kNE in all tissues tested (P less than 0.05) except muscle, spleen, and posterior left ventricle. Cholinergic muscarinic presynaptic restraint on kNE was detected during hypoxia only in the left atrial appendage and lung (P less than 0.05). These data indicate that hypoxia increases kNE in the heart, but restraint by cholinergic muscarinic and alpha 2-adrenergic presynaptic mechanisms limits increases in neurotransmitter synthesis and noradrenergic activation regionally.

Animals↗

PubMed1990

Sympathetic activation in dogs with congestive heart failure caused by chronic mitral valve disease and dilated cardiomyopathy.

Baseline plasma norepinephrine (NE) and epinephrine (EPI) concentrations were measured in dogs with naturally acquired heart failure (HF) caused by either degenerative mitral valve disease and mitral regurgitation (MR) or idiopathic dilated cardiomyopathy (DCM). Compared with controls (clinically normal), dogs with HF had increased plasma NE concentration, which was correlated positively with clinical severity of HF. Dogs with the most severe degree of HF (New York Heart Association functional class IV) had mean NE concentration significantly (P less than 0.05) greater than that of dogs with all other functional classes of HF. Overall, mean NE concentration in dogs with DCM was greater than that in dogs with MR. Plasma EPI concentration was not different between control dogs and dogs with HF or between dogs with DCM or MR. Correlations were not found between the echocardiographically derived end systolic volume index (used as an estimate of myocardial function) and plasma NE and EPI concentrations or serum sodium or potassium concentration. Dogs with DCM, as a group, had a small but significant (P less than 0.05) decrease in serum sodium concentration, compared with dogs with MR. This difference was maintained only for class-IV HF when dogs were separated according to functional HF class. In dogs with DCM, significant inverse correlation was found between plasma NE and serum sodium concentrations. When grouped together, all dogs with HF maintained this relationship; however, dogs with MR did not have correlation between plasma NE and serum sodium concentrations. Plasma EPI and serum sodium concentrations were not correlated for any group. It was concluded that in dogs, plasma NE, but not EPI, concentration is high in relation to the clinical severity of naturally acquired HF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Innervation patterns of the middle cervical--stellate ganglion complex in the rat.

The present experiments were designed to clarify the distribution of innervation of the middle and inferior cervical ganglia in the rat (middle cervical-stellate ganglion complex), the sympathetic ganglia which give rise to virtually all cardiac sympathetic nerves. Seven or 28 days after middle cervical-stellate ganglionectomy (surgical sympathectomy) norepinephrine content was measured in 9 peripheral areas including both the left and right atria and ventricles of the heart. The results were also compared to chemical sympathectomy produced with 6-hydroxydopamine. Seven or 28 days after surgical sympathectomy norepinephrine concentrations were reduced in all cardiac regions by at least 94%. Norepinephrine concentration in sub-diaphragmatic (spleen), but not supra-diaphragmatic (left intrascapular fat, left forelimb muscle), non-cardiac organs was preserved at control levels. 6-Hydroxydopamine treatment significantly reduced the norepinephrine concentration in all of the cardiac and non-cardiac tissues. The present evidence indicates that the middle cervical-stellate ganglion complex in the rat projects to a rather limited number of peripheral organs. Additionally, surgical sympathectomy produces more selective cardiac sympathectomy than 6-hydroxydopamine.

Animals↗

PubMed1990

Postsynaptic alpha- and beta-adrenergic supersensitivity of recovery properties in the canine ventricle.

We studied postsynaptic manifestations of adrenergic supersensitivity in the canine left ventricle (LV) regionally denervated by phenol in 14 dogs. Measurements were performed from 17 to 23 days later under alpha-chloralose anesthesia after sinoaortic denervation and vagotomy. After the sternum was split, multipolar pacing and recording electrodes were placed in both innervated and denervated LV. With isoproterenol infusion at 0.1, 1, and 10 micrograms/min, there was no change in activation times or pacing threshold. However, supersensitivity was manifested by a parallel left shift in the isoproterenol dose to effective refractory period (ERP) response curve (greater than or equal to 5.7 ms) in the denervated endocardium and epicardium compared with the respective innervated LV (P less than 0.05). In addition, local repolarization in the denervated area shortened more than the innervated area with isoproterenol infusion and correlated (r = 0.56) with the change in ERP. Postsynaptic supersensitivity of Purkinje to isoproterenol was also manifested by a parallel left shift (greater than or equal to 10 ms) in the dose to relative refractory period response curve in the denervated compared with the innervated area (P less than 0.05). In addition, a greater prolongation of Purkinje refractoriness was observed with phenylephrine only at 50 micrograms.kg-1.min-1. We conclude that postsynaptic supersensitivity occurred with the beta-agonist isoproterenol in both muscle and Purkinje. However, only Purkinje in the denervated area demonstrated an enhanced response to the alpha-agonist phenylephrine.

Animals↗

PubMed1990

Ventricular hypertrophy and presynaptic regulation of sympathetic function.

In normal heart, presynaptic cholinergic muscarinic and alpha 2-adrenergic mechanisms contribute to regional variations in the rate constant of norepinephrine turnover (kNE), an index of sympathetic neural function. To evaluate these mechanisms in the hypertrophied heart, pulmonary artery-constricted and sham-operated guinea pigs were pretreated with 1) saline vehicle (control) or 2) a combination of quinuclidinyl benzilate (Q), a muscarinic cholinergic antagonist, and yohimbine (Y), an alpha 2-adrenergic antagonist. An increase in kNE was determined in multiple regions of heart from incorporation of radiolabeled tyrosine into norepinephrine during a control period at 24 degrees C and again at 4 degrees C. In sham animals, kNE during cold stress was increased significantly (P less than 0.05) by Q + Y compared with vehicle, confirming that muscarinic cholinergic and/or alpha 2-adrenergic receptors exert a negative-feedback influence on sympathetic neurotransmitter synthesis. In pulmonary artery-constricted animals, in contrast, there were smaller increases in cardiac kNE compared with sham guinea pigs given Q + Y and subjected to cold stress. These data support the concept that muscarinic cholinergic and/or alpha 2-adrenergic presynaptic regulation of cardiac sympathetic function is altered in the hearts and vasculature of pulmonary artery-constricted guinea pigs.

Animals↗

PubMed1989

Organization of the sympathetic postganglionic innervation of the rat heart.

The origins and organization of cardiac sympathetic postganglionic nerves in the rat were identified in the present investigation. The retrograde tracer, Diamidino Yellow, was injected into the right or left ventricles to label somata in the sympathetic chain. Analysis of all sympathetic ganglia from superior cervical ganglion through the 10th thoracic ganglion indicated that the postganglionic innervation of the rat cardiac ventricles originates bilaterally. The majority of these somata were located in the middle and inferior cervical ganglia (middle cervical-stellate ganglion complex) (approximately 92% of all labelled cells), with lesser contributions from the superior cervical and 4th through 6th thoracic ganglia. To confirm and further quantitate these findings, the middle cervical-stellate ganglion complex was removed (MC-S ganglionectomy) bilaterally or ipsilaterally from the left or right sides, and regional cardiac norepinephrine concentration (left and right atrial appendages and left and right ventricles) was analysed 7 or 28 days later. At both times after bilateral MC-S ganglionectomy, regional cardiac norepinephrine was reduced by 89% to 100%, indicating the removal of almost all cardiac noradrenergic cells of origin and possibly fibers of passage. The results of unilateral MC-S ganglionectomy experiments indicated that the atrial appendages and the left ventricle receive bilateral innervation from the middle cervical-stellate ganglion complex. However, the left middle cervical-stellate ganglion complex appears to contribute a majority of the norepinephrine to the right ventricle. Furthermore, between 7 and 28 days after contralateral MC-S ganglionectomy, atrial appendages, but not ventricles, display significant recovery of norepinephrine content. The present data demonstrate: (1) a bilateral locus of origin of cardiac sympathetic postganglionic neurons, limited longitudinally to cervical through mid-thoracic ganglia, and (2) the ability of the cardiac postganglionic innervation to regenerate after partial denervation. These results demonstrate anatomical evidence for significant bilateral integration of cardiac sympathetic activity at the level of the sympathetic ganglion in the rat.

Amidines↗

PubMed1989

Altered peripheral noradrenergic activity in intact and sinoaortic denervated Dahl rats.

Development of salt-induced hypertension in Dahl salt-sensitive (S) rats is dependent on sympathetic overactivity which may be partially related to arterial baroreflex dysfunction and, therefore, is regionally selective. Our first experiment was designed to determine which regions have elevated sympathetic activity in Dahl S compared with Dahl salt-resistant (R) rats. Weanling (4-week-old) female Dahl R and S rats were fed low or high salt diets (0.13% and 8% NaCl) until 10 weeks of age. Norepinephrine (NE) synthesis was blocked with alpha-methyl-p-tyrosine, and the fractional decline of NE concentration was measured in various tissues. Dahl S rats with increases in both arterial pressure and left ventricular weight demonstrated increased NE turnover in the sinoatrial node, the atrial appendages, the cardiac ventricles, and the renal cortex. In all of these tissues except the cardiac ventricle, increases were associated with high salt intake. Our second experiment was designed to test if arterial baroreflex dysfunction could account for regional increases in sympathetic activity. Separate groups of Dahl R and S rats fed high salt were subjected to either sham surgery or sinoaortic baroreceptor denervation 1 week prior to turnover determinations. Sinoaortic baroreceptor denervation abolished differences in NE turnover between salt-fed Dahl R and S rats in the cardiac sinoatrial node and the atrial appendages, but not in the cardiac ventricles and the renal cortex. Sinoaortic baroreceptor denervation also abolished differences between salt-fed Dahl S and R rats in the spleen but not the duodenum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Central noradrenergic activity in intact and sinoaortic denervated Dahl rats.

Lesions in forebrain areas richly innervated by noradrenergic terminals and involved in cardiovascular function reduce or prevent hypertension in the Dahl salt-sensitive (S) rats fed a high (H) salt diet. This led us to examine two questions. (1) Is the noradrenergic activity altered in discrete forebrain and brainstem areas of SH rats? (2) Are these changes in noradrenergic activity eliminated by sinoaortic denervation (SAD)? Studies were done in 10-week-old female SH and Dahl salt-resistant (RH) rats. Half of the rats in each group had SAD surgery 1 week prior to study. An index of norepinephrine (NE) turnover was determined by measuring the decline in tissue NE concentration 8 h after administering alpha-methyl-p-tyrosine, a NE synthesis blocker, to animals from each of four groups: sham-RH, SAD-RH, sham-SH, and SAD-SH (n = 18-20 per group). Various discrete brain areas were obtained using the "punch technique." In SH rats the index of NE turnover was increased in the median preoptic nucleus and decreased in the paraventricular nucleus compared with RH rats regardless of SAD. In contrast, in SH rats the index of NE turnover was increased in the supraoptic nucleus and locus ceruleus compared with RH rats; however, SAD-RH had greater turnover of NE at these sites than SAD-SH. In summary, changes in noradrenergic activity in the median preoptic nucleus and the paraventricular nucleus may be related to genetic predisposition to hypertension in SH rats. In contrast, changes in the locus ceruleus and the supraoptic nucleus of SH rats may be related to impaired baroreflexes and thereby contribute to hypertension.

Animals↗

PubMed1989

Subendocardial infarction produces epicardial parasympathetic denervation in canine left ventricle.

Forty dogs underwent anterior descending coronary artery dissection with most having occlusion that was either maintained or reperfused. Study was performed 1-4 days later. Multiple electrodes placed in normal and ischemic zones were used to determine the depth of the epicardial rim overlying a subendocardial infarction. This was done by comparing voltage differential with respect to time (dV/dt) measurements of sequential bipolar electrograms along each needle. By this means, test sites with a rim were documented, and depths of epicardial biopsies for choline acetyltransferase were chosen. Epicardial effective refractory period (ERP) responses to vagal nerve stimulation were measured. In sham-operated controls, vagal stimulation prolonged ERP, and choline acetyltransferase activity was equivalent in all sites. In contrast, dogs with all durations of coronary occlusion and various thicknesses of subendocardial infarction had no significant prolongation of ERP limited to rim sites overlying the infarct during vagal nerve stimulation. Corresponding choline acetyltransferase activity was decreased in rim sites compared with remote areas. In addition, dogs given norepinephrine or physostigmine (to potentiate parasympathetic responses) did not demonstrate significant ERP prolongation with vagal stimulation. Infusion of acetylcholine into the distal ligated coronary artery produced dose-dependent prolongation of ERP in sites overlying the infarct. These data taken together support the hypothesis that subendocardial infarction, regardless of its homogeneity or thickness, produces parasympathetic denervation of the overlying epicardial rim.

Animals↗

PubMed1988

An electronic, negative feedback device to control arterial pressure.

Cardiovascular investigations frequently require manipulation of the arterial pressure for assessment of neural reflexes. This has largely been accomplished in the past by a bolus injection or constant infusion of a vasoactive drug. The purpose of the present investigation was to develop a proportional, integrative, negative feedback device capable of controlling arterial pressure in rats by modulating the infusion rate of the vasoconstrictor, phenylephrine. The device was designed to 1) maintain arterial pressure at a constant plateau level above the prevailing control pressure and 2) create linear ramp increases in arterial pressure. We have validated this system with conscious and urethan-anesthetized rats instrumented with arterial cannulas for arterial pressure measurement and aortic or venous cannulas for phenylephrine infusion. When used to create steady-state changes in blood pressure at 150 mmHg, the device maintained arterial pressure within +/- 7 mmHg of the desired level for the 20-min experimental periods. When used to create rising arterial pressure ramps (duration: 60 s; magnitude: 30 mmHg), regression analysis of the pressure vs. time relationship indicated that the correlation coefficient was greater than 0.99 in 90% of the trials, indicating a linear ramp. This device will aid in future cardiovascular protocols, especially in the analysis of baroreflex sensitivity.

Animals↗

PubMed1987

Location, distribution and projections of intracardiac ganglion cells in the rat.

Physiological studies indicate that cardiac parasympathetic nerves may act selectively at discrete cardiac sites. To determine anatomical sites at which selective integration of cardiac nerve activity may occur, the present study identified and described the location, distribution, and projections of intracardiac ganglion cells in the rat. The estimated 3992 ganglion cells per rat heart were located in 4 distinct groups, all above the atrioventricular groove: (1) between the superior vena cava and aorta (2.5% of total), (2) in the region of the superior interatrial septum (49.9%), (3) posterior to the left atrium (24.0%), and (4) posterior to the inferior interatrial septum and right atrium (23.5%). Only a few ganglion cells were located subepicardially within the infolding of the dorsal interatrial septum. Retrogradely transported fluorescent tracers injected into the left or right ventricles demonstrated that different groups of ganglion cells projected to discrete or selective regions of the heart. Projections to the left ventricle originate only from ganglion cells located posterior to the interatrial septum and the left atrium. In the rat, intracardiac ganglion cells, confined to 4 atrial regions, appear to have discrete sites of termination within the heart. It is proposed that selective activation of different intracardiac ganglion cell groups may elicit specific regional changes in cardiac parasympathetic nerve activity.

Animals↗

PubMed1987

Effects of intravenous infusions of vasopressin and angiotensin II on central and peripheral noradrenergic function in conscious rabbits.

Vasopressin (AVP) and angiotensin II (AII) are proposed to exert part of their cardiovascular effects via different actions within the central nervous system. These peptides are also known to alter central noradrenergic function. In the present study we determined the effects of these peptides administered intravenously on norepinephrine (NE) turnover in discrete brain regions thought to be involved in the regulation of circulation, and simultaneously, in various peripheral tissues. An index of NE turnover was determined by measuring the decline in tissue NE concentration 75 min after administration of alpha-methyl tyrosine (240 mg . kg-1 . min-1, i.p.). During NE synthesis blockade, five separate groups of rabbits were infused intravenously (1 h) with either saline, AVP (4 and 16 mU . kg-1 . min-1), AII (0.1 microgram . kg-1 . min-1), or phenylephrine (PE) (5 micrograms . kg-1 . min-1). The low dose of AVP produced an increased index of NE turnover in the median preoptic area and the paraventricular nucleus, and concomitantly, a decreased index of NE turnover in kidney and skeletal muscle. In contrast, AII produced an increased index of NE turnover in the locus ceruleus and the intestine. Neither the infusion of vehicle nor the infusion of phenylephrine, which increased arterial pressure comparable to AVP and AII, produced detectable changes in indices of central and peripheral norepinephrine turnover. A higher dose of AVP produced a different pattern of changes in NE turnover than the low dose. These results demonstrate that intravenous infusion of the low dose of AVP produced changes in noradrenergic function in specific central areas known to be involved in autonomic outflow.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1987

Choline and acetylcholine concentration in transplanted rat heart.

A liquid chromatographic assay was used to determine the choline and acetylcholine concentrations in the four chambers of rat hearts 2, 4, and 8 days after transplantation into an abdominal site. Corresponding measurements were made in the hearts of host rats. We found regional cardiac acetylcholine concentrations in controls follow the nonuniform pattern seen with choline acetyltransferase (CAT) activity, being highest in the atria (8-12 nmol/g) and lower in the ventricles (0.7-1.6 nmol/g). Following transplantation, acetylcholine levels decreased significantly only in the right ventricle after 8 days. Following a unilateral vagotomy (random, left or right), acetylcholine concentrations in the distal portion of the severed nerve decreased to half the value of the intact contralateral side by 4 days. The continued presence of acetylcholine, despite significantly reduced CAT activity in the severed nerve and transplanted heart, suggests that acetylcholine is preserved, perhaps by vesiculation in nonstimulated postganglionic terminals. The localized decrease in acetylcholine in the right ventricle after 8 days suggests that transplantation may interrupt the postganglionic fibers to this area.

Acetylcholine↗

PubMed1987

Effects of chronic progressive myocardial hypertrophy on indexes of cardiac autonomic innervation.

The development of cardiac hypertrophy is associated with marked changes in cardiac autonomic innervation. Significant and sustained reductions of myocardial catecholamine stores and activities of tyrosine hydroxylase and dopamine beta-hydroxylase have been reported in models of acutely induced ventricular hypertrophy. Conversely, activity of choline acetyltransferase, a marker of parasympathetic nervous function, shows transient increases during the development of acute right ventricular hypertrophy. The potential physiological importance of these changes prompted us to examine a clinically more relevant model of slowly progressive ventricular hypertrophy. Application of a loose band around the pulmonary artery of weanling guinea pigs resulted in a growth-related progressive right ventricular pressure overload. Right ventricular weight-to-body-weight ratio was increased significantly and progressively at 9 and 18 weeks in banded animals (0.92 +/- 0.05 and 1.31 +/- 0.11 mg/g, respectively, p less than 0.01) compared with sham-operated controls (0.55 +/- 0.02 and 0.59 +/- 0.01 mg/g, respectively) but showed no further gain at 27 weeks (1.41 +/- 0.10 mg/g). Activities of tyrosine hydroxylase and dopamine beta-hydroxylase remained unchanged in all experiment groups, while right ventricular contents of norepinephrine in banded animals at 18 and 27 weeks exhibited sustained and progressive increases (2.45 +/- 0.11 and 3.40 +/- 0.19 micrograms/right ventricle, respectively) over controls (1.80 +/- 0.13 and 2.40 +/- 0.22 micrograms/right ventricle, respectively, p less than 0.01). The activity of choline acetyltransferase was markedly elevated in banded animals at 18 weeks (32.6 +/- 2.7 nmol/hr/right ventricle) but returned to baseline by 27 weeks (22.8 +/- 1.4 nmol/hr/right ventricle).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Role of myocardial hypertrophy in trophic stimulation of indices of sympathetic cardiac innervation.

Indices of cardiac sympathetic innervation have commonly been found depressed in the failing, hypertrophied heart. In contrast, we have recently demonstrated that hemodynamically compensated, very gradually developing right ventricular hypertrophy is associated with an increase in sympathetic nervous markers. The present experiments were performed to corroborate these findings in a model of acutely induced right ventricular hypertrophy, and to further characterize changes in markers of autonomic innervation associated with cardiac hypertrophy. Male guinea pigs underwent either pulmonary artery banding (P) with an acutely constricting ligature, or bilateral stellate ganglionectomy (S), or both (PS). Appropriate sham procedures were performed in animals subjected to only one intervention; controls (C) underwent sham-S and sham-P. Groups of animals were sacrificed at 10 and 20 days after surgery. Cardiac tissues were weighed and subsequently analyzed for activities of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH), two enzymes catalyzing the biosynthesis of catecholamines (CAs), and of choline acetyltransferase (CAT), a marker of parasympathetic activity, as well as for norepinephrine (NE). S resulted in profound depletions of cardiac NE of 88-92% and in significant decreases in the activities of DBH and TH. Marked right ventricular hypertrophy developed rapidly following P, and was not modified by S. Similar to our previous results, acute right ventricular hypertrophy was associated with moderate increases (10-20%) of sympathetic markers; following S, these increases (of presumably residual sympathetic innervation) were greatly enhanced, amounting to 171% and 105% for NE at 10 and 20 days, respectively. In contrast, sympathetic markers in the left ventricle of stellatectomized animals were not affected by P. Activity of CAT remained unaltered by the experimental interventions. Our experiments indicate that increases in markers of sympathetic innervation may be a common feature of the early, compensated stage of cardiac hypertrophy, regardless of its time course. Sympathetic neural mechanisms do not appear to play a stimulatory or trophic role in the hypertrophic process. Conversely, they seem to be secondary in nature, suggesting a possible stimulatory influence of hypertrophying myocardium on sympathetic cardiac nerves.

Animals↗

PubMed1987

Select cardiovascular and metabolic responses of diabetic rats to moderate exercise training.

The combined influence of diabetes and moderate treadmill exercise training on select metabolic and cardiovascular parameters was investigated with mature male Sprague-Dawley rats assigned to either control diabetic or diabetic groups receiving exogenous insulin. Experimental diabetes was induced with streptozotocin (80 mg.kg-1, i.v.) and verified by blood glucose concentrations greater than 16 mmol. The animals were designated as control, insulin-injected (5 U.kg-1, twice daily), or saline-injected (twice daily), and assigned to either non-trained or trained sub-groups. Insulin treatment partially restored the measured physiological functions to within normal limits. All animals were trained at 60 to 70% maximal oxygen consumption for 9 wk and exhibited higher maximal oxygen consumption values and cytochrome oxidase activity of the soleus muscles. Diabetes caused lower (P less than 0.05) reductions in resting heart rate but training-induced bradycardia did not occur in any group. Heart rate response to atropine sulfate (1 mg.kg-1, atrial choline acetyltransferase activity, atrial acetylcholine concentration, and quinuclidinyl benzilate binding was measured to evaluate changes in the parasympathetic nervous system. Atropine-induced cardiac acceleration was most pronounced in control and least effective in diabetic animals. Endurance training had no meaningful influence on this response to cholinergic inhibition. Quinuclidinyl benzilate binding for the diabetic and the diabetic groups receiving insulin revealed no change in receptor number, receptor affinity, or training effects. These findings indicated that 9 wk of exercise training improves the aerobic capability of insulin-deficient rats without changing cardiovascular characteristics associated with the parasympathetic nervous system.

Acetylcholine↗

PubMed1986

Facilitation of baroreflex-induced bradycardia by stimulation of specific hypothalamic sites in the rat.

Hypothalamic stimulation generally inhibits baroreflex-induced bradycardia. However, we have noted discrete areas of the rat hypothalamus which facilitate reflex bradycardia. The effects of hypothalamic stimulation on baroreflex-induced changes in heart rate were investigated in urethane-anesthetized rats (1.2 g/kg, i.p.; n = 6) instrumented with femoral arterial and venous catheters. Bipolar electrodes (250 micron diameter) were implanted stereotaxically in the hypothalamus. Baroreflex-induced bradycardia was elicited by phenylephrine (PE) injection (8-20 micrograms/kg). Responses to stimulation (STIM) (50-150 microA, 80 Hz, 0.5 ms), PE, and Stim + PE were studied for 1 min. In the ventral medial and anterior hypothalamus, STIM caused transient increases in blood pressure and no changes in heart rate. Peak blood pressure was lower during STIM + PE than during PE (144 +/- 5 vs 164 +/- 3 mm Hg; P less than 0.05). However, STIM + PE resulted in a lower heart rate compared to PE (194 +/- 22 22 vs 270 +/- 17 bpm; P less than 0.05). At 1 min, the heart rate in STIM + PE rats remained lower than in PE rats (205 +/- 37 vs 319 +/- 16 bpm; P less than 0.05). Atropine administration indicated that the facilitation was primarily parasympathetic in nature. These results identify specific hypothalamic regions which facilitate baroreflex-induced bradycardia by parasympathetic mechanisms.

Animals↗

PubMed1986

A microcomputer program for determining turnover rates before and after intervention in a single animal.

A set of three programs to calculate the turnover of biomolecules whose metabolism follows a steady-state precursor-product relationship and follows the open, single-compartment kinetics model has been written in MS-BASIC. The programs comprise a system for determining two values of turnover, before and after an intervention which may alter the turnover rate, in a single animal. The programs have been extensively tested in our laboratory for the determination of norepinephrine turnover under differing physiological and pharmacological conditions. The utility of the programs lies in their ability to readily adapt to turnover determinations for any substance whose metabolic pathway conforms to the model constraints. This includes the biogenic amine neurotransmitters, peptides and proteins, and many small biological molecules or pharmacological agents.

Animals↗