Biomedical subjects

B L Pegram

Publications and source records attributed to B L Pegram.

At least 55 records · Page 3Linked to original sources

PubMed1984

Urapidil in normotensive and spontaneously hypertensive rats: the effects on systemic and regional haemodynamics and cardiac mass.

The effects of treatment for three weeks with urapidil (10 mg/kg p.o. twice daily) on systemic and regional haemodynamics and cardiac mass were studied in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Urapidil decreased mean arterial pressure and total peripheral resistance index (176 +/- 3 versus 145 +/- 5 mmHg and 0.61 +/- 0.02 versus 0.49 +/- 0.02 units, respectively; each P less than 0.01) in SHR without affecting heart rate, cardiac index or cardiac mass. No systemic haemodynamic changes were observed in WKY rats. All organ vascular resistances decreased significantly in SHR and blood flow increased to skin (P less than 0.01) and kidneys (P less than 0.05). These data indicate that urapidil is a potent antihypertensive agent in SHR which reduced mean arterial pressure through a decreased total peripheral resistance that was distributed throughout all circulations. Despite these haemodynamic changes, cardiac mass did not change.

Animals↗

PubMed1983

Cardiovascular adjustment to antiadrenergic agents.

A common target organ involvement associated with essential hypertension is left ventricular hypertrophy. A number of, but not all, effective antihypertensive drugs will regress left ventricular hypertrophy. Our attention has focused on the hemodynamic characteristics of those drugs that either directly or indirectly alter sympathetic nervous activity. alpha-Methyldopa has been widely studied in both experimental animals and hypertensive man and been found to be efficacious in lowering arterial pressure and regressing left ventricular hypertrophy. Another centrally acting antihypertensive drug, clonidine, produces similar hemodynamic effects but has no effect on left ventricular hypertrophy at similar hypotensive levels. Vasodilators such as hydralazine and minoxidil reflexly stimulate the sympathetic nervous system and may actually exacerbate left ventricular hypertrophy when given alone. In combination with beta adrenergic blocking agents, however, a reduction in both arterial pressure and cardiac mass may occur. Prolonged treatment with these antihypertensive agents had no detrimental effect on regional blood flows including myocardial flow. Ventricular performance studies indicate that regression of hypertrophy improves ventricular performance although the heart with regressed hypertrophy, when faced with an increased afterload, may still demonstrate impaired performance.

Adrenergic beta-Antagonists↗

PubMed1982

Effect of methyldopa, clonidine, and hydralazine on cardiac mass and haemodynamics in Wistar Kyoto and spontaneously hypertensive rats.

Prolonged treatment of spontaneously hypertensive (SHR) rats with either methyldopa or clonidine significantly and similarly reduced mean arterial pressure. Heart rate increased with methyldopa but decreased with clonidine; other haemodynamic effects were similar. SHR treated methyldopa, but not clonidine, had significantly reduced cardiac masses and heart weight to body weight ratios than did rats receiving the vehicle. Normotensive Wistar Kyoto (WKY) rats treated with methyldopa also had lower cardiac masses than their controls, but exhibited no significant changes in systemic haemodynamics. Treatment with the vasodilator hydralazine increased cardiac output and decreased total peripheral resistance in both SHR and WKY, but the decrease in mean arterial pressure was significant only in SHR. Heart rate was decreased and heart weight to body weight in WKY was elevated. Cardiac mass did not change. Minimal changes in regional haemodynamics were noted, with hydralazine eliciting a decrease in most organ vascular resistances. The data indicate that regression of hypertrophy following antihypertensive therapy was not solely dependent upon haemodynamic factors; nor was it necessarily the effect of suppression of the adrenergic system, since the results obtained with methyldopa and clonidine was similar.

Animals↗

PubMed1982

Hemodynamic studies in spontaneously hypertensive rats with congenital arteriovenous shunts.

Previous studies have demonstrated a subset of normotensive rats (Wistar-Kyoto, WKY) that has arteriovenous shunts and biventricular hypertrophy. In this study, using the combined radioactive reference sample and microsphere techniques, spontaneously hypertensive (SHR) and WKY rats were found to have arteriovenous fistulas, and the magnitude of this shunting was quantified. In both groups with shunts (WKY and SHR, respectively) mean arterial pressure was lower (117 +/- 3 vs. 125 +/- 2 mmHg, NS; 164 +/- 4 vs. 184 +/- 7 mmHg, P less than 0.001) and cardiac index was higher (518 +/- 52 vs. 259 +/- 10 ml.min-1.kg-1, P less than 0.001: 416 +/- 18 vs. 239 +/- 8 ml.min-1.kg-1, P less than 0.001) than in rats without shunts. Both groups demonstrated sizable shunts, with microsphere trapping in 55 +/- 6 and 47 +/- 5% in WKY and SHR, respectively, and reduced blood flow to every organ. These data demonstrate the need for caution in evaluating hemodynamic and myocardial functional data as well as endocrinologic or metabolic functions in WKY and SHR unless shunting is excluded. Moreover, since these subsets seem to have had arteriovenous shunts from birth, it may be inferred that the development of the arterial hypertension in SHR did not result from tissue hyperperfusion.

Animals↗

PubMed1981

Neuroeffector function of isolated portal vein from spontaneously hypertensive and wistar-kyoto rats: dependence on external calcium concentration.

The calcium dependence of the vascular neuroeffector function has been studied in the portal vein of spontaneously hypertensive Okamoto rats (SHR) and Wistar-Kyoto rats (WKY). The noradrenaline (NA) sensitivity of veins of both species, expressed in terms of ED50, was decreased to the same extent in relation to the reduction in Ca2+ ion concentration below 2.5 mM. The responses to individual NA concentrations at subnormal Ca2+ concentrations were better maintained, however, in portal veins from SHR than from WKY, indicating that the excitation contraction coupling mechanism is less dependent on external Ca2+ concentrations in the portal vein from SHR than from WKY. In both strains of rats the spontaneous myogenic activity of the vessel was depressed in low Ca2+ concentrations to a greater extent than responses to nerve stimulation, which, in turn, were more reduced than the excitatory responses to exogenous NA or acetylcholine (ACh). Transmitter release (fractional overflow of 3H-NA/impulse) was less dependent on Ca2+ concentrations than the contractile nerve stimulation response. The persistence of all responses in reduced Ca2+ concentrations was significantly greater in the portal vein of SHR. It is concluded that the phasic, spontaneously active smooth muscle of the rat portal vein is highly dependent on the external calcium concentration and that various induced responses persist to a varying degree in reduced Ca2+ concentrations. It is suggested that this is due to interference with electromechanical coupling as well as myogenic spread of activation. Induced responses of the portal vein from SHR are, in general, less affected by decreased Ca2+ concentrations than the WKY portal vein, indicating an altered vascular smooth muscle excitation-contraction coupling mechanism in spontaneous hypertension. Possibly an increased efficiency of the coupling mechanism may contribute to augment vascular responses in the development of hypertension and promote structural vascular changes.

Animals↗

PubMed1980

Systemic and regional haemodynamics in anterior hypothalamic hypertension in spontaneously hypertensive and Wistar-Kyoto rats.

1. Systemic and regional haemodynamics were determined in conscious Wistar-Kyoto and spontaneously hypertensive rats with the radioactive microsphere technique after sham lesion or bilateral electrolytic lesion of the nuclei of the anterior hypothalamus. 2. Anterior hypothalamic lesions produced an increase in blood pressure, heart rate and cardiac output. 3. In the rats with lesions there were changes in regional haemodynamics: heart and skeletal muscle flow increased; renal, skin ans splanchnic flow decreased. 4. The haemodynamic consequences of ablation of the anterior hypothalamus were similar in both normotensive Wistar-Kyoto and spontaneously hypertensive rats. The haemodynamic pattern resembles that seen during fighting and exercise.

Animals↗

PubMed1980

Disparate effects of methyldopa and clonidine on cardiac mass and haemodynamics in rats.

1. Wistar-Kyoto and spontaneously hypertensive rats were given either methyldopa (400 mg day-1 kg-1) or clonidine (0.1 or 0.3 mg day-1 kg-1) for 3 weeks commencing at 20 weeks of age. 2. Both drugs significantly decreased mean arterial pressure in spontaneously hypertensive but not Wistar-Kyoto rats. Heart rate was significantly increased in spontaneously hypertensive rats by methyldopa, whereas clonidine significantly decreased heart rate. The higher dose of clonidine also decreased heart rate in Wistar-Kyoto rats. Both cardiac output and total peripheral resistance decreased slightly, but not significantly, with both agents. 3. Methyldopa, but not the lower equipotent depressor dose of clonidine, reduced left ventricular hypertrophy in spontaneously hypertensive rats. However, the higher dose of clonidine also significantly decreased the heart to body weight ratio despite an increased total peripheral resistance presumably due to the alpha-adrenergic agonist effect. 4. Minimal changes in organ blood flows were noted with both drugs. 5. These results suggest that neither systemic haemodynamics nor central inhibition of adrenergic drive are primary factors responsible for the regression of hypertrophy.

Animals↗

PubMed1980

Reference sample microsphere method: cardiac output and blood flows in conscious rat.

Validation of the reference sample method (RSM) in the rat was accomplished by: 1) simultaneous measurement of cardiac output (CO) by the RSM and electromagnetic flowmetry method in ether-anesthetized open-chest Wistar rats, and 2) determination of systemic and regional hemodynamic reproducibility in conscious rats following three serial injections of microspheres. The optimal sampling time and sampling rate were determined in several CO states. The results indicate that: 1) 200 or more microspheres contained in the reference sample result in an accurate determination of CO, 2) almost 100% of the microspheres are trapped by tissues with in 20 s of cessation of the microsphere injection, 3) the hemodynamic steady state is affected only under low cardiac output conditions at a high sampling rate (1.211 ml/min), 4) three repeated injections of microspheres in conscious animals do not alter systemic hemodynamis, and 5) the reproducibility of regional blood flow distribution is good in all organs except the liver, stomach, spleen, and skin (third application). These data indicate that the RSM is reliable, providing reasonable accuracy and reproducibility of systemic and regional hemodynamics in the rat.

Animals↗

PubMed1976

Changes in the contractile response of arteires and veins from hypertensive rabbits to sympathetic nerve activity: assessment of some postsynaptic influences.

Contractile responses to field stimulation of intramural nerves of arteries and veins taken from rabbits made hypertensive by partial constriction of the abdominal aorta have been related to the carotid artery pressure. The increase in contraction of cephalic and short saphenous veins with rise in carotid artery pressure can be accounted for by an increase in sensitivity of the alpha-adrenergic receptor. The neurogenic contraction of the ear artery increased with carotid artery pressure rise. Changes in some of the extraneuronal factors that influence transmitter distribution and disposition in the tunica media were examined. In hypertensive animals, the percentage of released adrenergic transmitter entering the vessel wall might be expected to decrease due to an increase in medial thickness. However, this percentage was not significantly altered in the ear artery probably due, in part, to a concomitant increase in medial permeability to the transmitter. Extraneuronal transmitter disposition factors, i.e. extraneuronal uptake, monoamine oxidase, and catechol-O-methyltransferase activity are directly related to the wet weight of the vessel wall. Thus, their contribution to transmitter disposition would be expected to increase with increase in vessel wall thickness and tend to reduce the response to sympathetic activity. As the contractile response increased in the hypertensive vessels despite such changes, the increase in effector cell mass and density of neuronal terminal plexus, shown previously to increase with hypertension, are more important than these other considerations.

Animals↗

PubMed1976

Facial vein in the rabbit. Neurogenic vasodilation mediated by beta-adrenergic receptors.

A segment of the facial vein of the rabbit, that opposite the buccal cavity, responds to norepinephrine (NE) and opposite the buccal cavity, responds to norepinephrine (NE) and transmural nerve stimulation (TNS) by a brisk biphasic dilation. The dilation in response to both procedures is reveresed by prior exposure to propranolol (10(-6)M). Pretreatment with phenoxybenzamine (10(-5)M) increases the size of the neurogenic response and displaces the NE dose-relaxation curve to the left. Histamine causes a constrictor response exclusively. Sympathetic stimulation of a segment of the facial vein proximal to this buccal segment, and also of the external jugular vein, results in constriction. Light microscopy showed no fequtres which can account for the dilation, and fluorescence histochemistry using a modified Flack technique showed a dense adrenergic nerve plexus extending throughout the thickness of the media. We found that frequency-response characteristics and neuronal uptake of 3H-NE were consistent with findings for a blood vessel with a heavy medial innervation. Also, monoamine oxidase and catechol O-methyltransferase activities were similar to those found in other rabbit veins. Furthermore, these results are consistent with an adrenergic neuroeffector organization in which there is a predominance of beta- over alpha-adrenergic receptors. In conclusion, the presence of a dilator response in this buccal segment of the facial vein may be related to its location in the wall of the cheek, where it may be subjected to considerable stretch.

Adrenergic beta-Agonists↗

PubMed1975

Changes in left ventricular internal diameter with increasing pericardial pressure.

Changes in left ventricular internal diameter resulting from increasing intrapericardial pressure induced by increasing the pericardial fluid volume were studied in closed chest, anaesthetized dogs. Left ventricular internal diameters were measured by placing an ultrasonic dimension catheter in the left ventricle at the time of the experiments. With increasing pericardial pressure, significant increases occurred in heart rate and mean left atrial pressure. Left ventricular end-diastolic and end-systolic diameter progressively decreased as the pericardial pressure was elevated. After beta adrenergic blockade with propranolol (1 mg/kg), the decline in end-systolic diameter during pericardial tamponade was significantly reduced. These observations indicate the importance of the systolic reserve and the role of beta adrenergic receptors in the adaptation of the left ventricle to increases in pericardial tamponade.

Animals↗

PubMed1975

An evaluation of the pericardial sac as a safety factor during tamponade.

Studies were conducted in vitro to determine the permeability characteristics of the rabbit and dog pericardium. The hydraulic conductance (Lp), which was significantly higher than other tissue, was 1.6 +/- 0.19 X 10(-4) and 1.78 +/- 0.18 X 10(-4) g-cm-2-min-1-cm H2O-1 (mean +/- SEM), respectively, for the rabbit and dog pericardium. For various solutes, the permeability coefficient (P) of the pericardium for the rabbit was: 1.40 +/- 0.10 X 10(-4) cm-s-1 for water, 0.50 +/- 0.03 X 10(-4) cm-s-1 for glucose, and 0.73 +/- 0.005 X 10(-4) cm-s-1 for albumin. The reflection coefficient, sigma, for various solutes was: glucose 8.89 +/- 0.86 X 10(-4), sucrose 15.7 +/- 1.5 X 10(-4), dextran (molecular weight 40 000) 0.39 +/- 0.03, albumin 0.42 +/- 0.05, and for haemoglobin 0.58 +/- 0.06. These results, which indicate that the pericardium offers little resistance to the bulk transfer of liquids and to the passage of large molecules, are discussed as possible safety factors during pericardial effusion.

Albumins↗

PubMed1975

Vasomotor nerve control of isolated arteries and veins.

In order to compare neuro-effector function in different blood vessels, frequency-response relationships were determined for the following preparations: 1)Isolated rings of the proximal saphenous, distal saphenous and ear arteries, the parietal branch of the internal iliac vein and the small saphenous vein from the rabbit, 2) spiral strips of the rabbit pulmonary artery and 3) longitudinal preparations of the rat portal vein. In each rabbit tissue only one low (less than or equal to 4 Hz) and one high (larger than or equal to 8 Hz) transmural nerve stimulation frequency was applied until steady state responses were obtained and these were expressed as a percentage of a maximum response to exogenous noradrenaline (NA) applied in each experiment. The general shape of the frequency-response curves was similar, but differences in steepness and amplitude of the maximum neurogenic response relative to exogenous NA were found. The steepness of the frequency-response relationships of the veins tended to be greater than those of the arteries. It appears that factors such as close neuro-muscular contacts, presence of terminal nerve fibres within the media and the operation of mechanisms for myogenic propagation of activity contribute to the effectiveness of neurogenic vascular control as revealed by frequency-response curves. In vivo, geometrical factors can greatly augment the hemodynamic significance of the observed differences.

Animals↗

PubMed1975

Analysis of changes in reactivity of rabbit arteries and veins two weeks after induction of hypertension by coarctation of the abdominal aorta.

Vessel dimensions and characteristic responses to norepinephrine were measured in various arteries and veins of the rabbit made hypertensive by partial constriction of the upper abdominal aorta. The ear, radial, and basilar arteries taken from the circulation proximal to the ligature (the hypertensive arteries) were thickened in proportion to the rise is arterial blood pressure. The water, sodium, and potassium contents of these and all other vessels were not significantly changed in the hypertensive rabbits. The maximum response to norepinephrine in the ear artery, a representative vessel from the hypertensive part of the rabbit, was increased, whhereas the sensitivity of this vessel to norepinephrine expressed as the ED50 did not alter with changes in the arterial blood pressure. In contrast, the thickness and the maximum response to norepinephrine of the saphenous artery, representative of vessels distal to the ligature (normotensive vessels) and of the saphenous and cephalic veins were unaltered. The sensitivity as indicated by the norepinephrine ED50 of the veins, but not of the saphenous artery, increased with a rise in carotid artery blood pressure. These results suggest that the increased responsiveness to norepinephrine of arteries proximal to the ligature is due to changes in muscle mass and that the increased responsiveness of the veins is due to increased sensitivity to norepinephrine.

Animals↗

PubMed1975