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Biomedical subjects

M D Thames

Publications and source records attributed to M D Thames.

At least 91 records · Page 5Linked to original sources
PubMed1982

Baroreflex regulation of renal nerve activity during volume expansion.

Volume expansion could inhibit renal nerve activity by stimulating cardiopulmonary baroreflexes or by increasing arterial pressure (i.e., stimulating the sinoaortic baroreflexes). Our study assessed the relative roles of these two reflexes in the renal nerve activity responses to volume expansion (15 ml/kg 6% dextran in normal saline). With cardiopulmonary and arterial baroreflexes intact, volume expansion resulted in increases in arterial pressure and pulmonary artery wedge pressure and in decreases in renal nerve activity. After sinoaortic denervation, volume expansion resulted in similar decreases in renal nerve activity for similar increases in pulmonary artery wedge pressure. In contrast, after selective vagotomy (sinoaortic baroreflexes intact) volume expansion resulted in increases in arterial pressure and pulmonary artery wedge pressure, but reductions in renal nerve activity were markedly attenuated. After sinoaortic denervation and vagotomy, volume expansion did not result in significant changes in renal nerve activity. We conclude that decreases in renal nerve activity during volume expansion are mediated mainly by cardiopulmonary receptors with afferent vagal fibers. Sinoaortic baroreceptors appear to play a minor role in mediating these responses.

Animals↗
PubMed1982

Sensitization of vagal cardiopulmonary baroreflex by chronic digoxin.

It has been recently reported that intracoronary acetylstrophanthidin injection acutely sensitizes the cardiac baroreflex (vagal afferents). We wondered whether chronic administration of digoxin also augmented the gain of this reflex. We treated seven dogs with digoxin intravenously (40 micrograms/kg loading dose followed by 15 micrograms.kg-1.day-1) for 7 days; eight additional dogs received vehicle for 7 days. With the dogs under chloralose anesthesia, we assessed the changes in renal nerve activity that resulted from stimulation of cardiopulmonary receptors with volume expansion (15 ml/kg of 6% dextran in saline) in digoxin- and vehicle-treated groups under control conditions, after sinoaortic denervation (SAD), and after SAD plus vagotomy. Under control conditions volume expansion resulted in decreases of renal nerve activity of 13.5 +/- 3.5%/mmHg increase in pulmonary artery wedge pressure in digoxin-treated dogs. This tended to be greater than the response of sham-treated dogs (-9.5 +/- 1.5%/mmHg increase). After SAD, renal nerve activity decreased 19 +/- 5%/mmHg increase in pulmonary artery wedge pressure in the digoxin group compared with only 8 +/- 1%/mmHg increase in the vehicle group. These responses were significantly different. The plasma digoxin level in the digoxin-treated group was in the therapeutic range (1.9 +/- 0.4 ng/ml). Vagotomy abolished the responses to volume expansion in both groups. Thus chronic digoxin treatment resulting in therapeutic plasma levels of digoxin sensitizes vagal afferents mediating the cardiopulmonary baroreflex influence on renal nerve activity.

Animals↗
PubMed1982

Role of macula densa in renal nerve modulation of renin secretion.

Low-frequency renal nerve stimulation (0.25 Hz) augments the renin secretion response to reduction of renal perfusion pressure to 50 mmHg by aortic constriction. The present experiments determined whether this modulating influence could be demonstrated when the macula densa receptor was inoperative. In 10 anesthetized dogs with a nonfiltering kidney and sectioned renal nerves, aortic constriction to 52 mmHg decreased renal blood flow and increased renin secretion from 126 +/- 94 to 192 +/- 55 ng/min. During low-frequency renal nerve stimulation and aortic constriction to 50 mmHg, renin secretion was not augmented (37 +/- 13 to 81 +/- 42 ng/min). In four anesthetized dogs with nonfiltering kidneys, aortic constriction to 52 mmHg increased renin secretion similarly before (16 +/- 8 to 68 +/- 17 ng/min) and after renal denervation (14 +/- 14 to 78 +/- 18 ng/min). Therefore, the augmentation of the renin secretion response to aortic constriction to 50 mmHg by low-frequency renal nerve stimulation in filtering kidneys does not result from an interaction with the renal vascular baroreceptor or the juxtaglomerular granular cells. Since neural augmentation of renin secretion during aortic constriction was not observed in the nonfiltering kidney where the macula densa is inoperative, we conclude that the macula densa is the probable site for the neural modulation of renin secretion.

Animals↗
PubMed1982

Role of renal alpha-adrenoceptors mediating renin secretion.

The increase in renin secretion resulting from low-frequency renal nerve stimulation (0.5 Hz) occurs in the absence of changes in urinary sodium excretion or renal blood flow and is apparently derived from a direct effect of renal sympathetic nerves on juxtaglomerular granular cells. We sought to determine the role of renal alpha-adrenoceptors in this neurally evoked renin secretion. The neurally evoked renin secretion was unaffected by renal alpha-adrenoceptor blockade with phentolamine or prazosin; however, two dose levels of phenoxybenzamine equally inhibited the renin secretion. The renal vasoconstrictor response to graded renal nerve stimulation was similarly diminished by phentolamine, prazosin, and the higher phenoxybenzamine dose, whereas the lower phenoxybenzamine dose was significantly less effective. Renal alpha-adrenoceptor stimulation with methoxamine infusion at doses that were just subthreshold for altering renal blood flow and urinary sodium excretion or at doses that just reduced urinary sodium excretion also did not change renin secretion. Higher doses of methoxamine that decreased both renal blood flow and sodium excretion increased renin secretion. Based on the inability of phentolamine and prazosin to prevent neurally mediated renin secretion and on the dose-response relationship between methoxamine and changes in renin secretion, renal blood flow, and urinary sodium excretion, we conclude that renal alpha-adrenoceptors do not mediate renin secretion elicited by direct neural activation of the juxtaglomerular granular cells. The data suggest that phenoxybenzamine inhibits neurally mediated renin secretion by a mechanism other than renal alpha-adrenoceptor blockade.

Adrenergic alpha-Antagonists↗
PubMed1982

Differential baroreflex control of heart rate and vascular resistance in rabbits. Relative role of carotid, aortic, and cardiopulmonary baroreceptors.

We assessed the relative roles of aortic (ABR), carotid sinus (CBR), and vagal cardiopulmonary baroreceptors in the reflex control of heart rate and vascular resistance during changes in arterial blood pressure. Injections of phenylephrine (PE) and nitroglycerin (NG) were given intravenously to anesthetized rabbits (chloralose-urethane). Reflex, heart rate responses were impaired significantly by denervation (X) of either CBR or ABR. In contrast, reflex vascular responses in the hindlimb (perfused at constant blood flow) were preserved except for a slight impairment of reflex vasoconstriction after ABRX. Vagotomy with intact CBR and ABR impaired only the reflex bradycardia. After vagotomy, neither CBRX nor ABRX altered significantly the reflex heart rate or vascular responses except, again, for an impairment of reflex vasoconstriction after ABRX. Combined CBRX and ABRX eliminated all reflex responses except for a small bradycardia and a biphasic change in perfusion pressure (constrictor-dilator) during PE. Vagotomy eliminated the bradycardia and the dilator phase; the constrictor phase persisted and was abolished by lumbar sympathectomy. The results indicate that (1) reflex control of heart rate may be impaired when reflex control of hindlimb resistance is preserved; thus reflex changes in heart rate may not be used as a reliable index of the integrity of arterial baroreceptor control of the total circulation; (2) one set of arterial baroreceptors does not compensate for the absence of the other with respect to activation of vagal neurons; in contrast, one set of baroreceptors compensates fully for the absence of the other with respect to inhibition of sympathetic neurons; (3) cardiopulmonary and other baroreceptors contribute minimally to reflex responses only during large PE-induced increases in arterial pressure.

Afferent Pathways↗
PubMed1981

Baroreflex control of heart interval in conscious renal hypertensive dogs.

The purpose of this study is to determine if baroreflex control of heart interval is abnormal in conscious dogs with renal hypertension. Changes in heart interval in response to transient nitroglycerin-induced decreases in arterial pressure and transient phenylephrine-induced increases in arterial pressure were determined in nine normotensive [mean arterial pressure 92 +/- 4 (SE) mmHg] and nine renal hypertensive conscious dogs (mean arterial pressure 139 +/- 10 mmHg). Data were acquired before and after beta-adrenergic blockade with 2 mg/kg iv propranolol and before and after parasympathetic blockade with 0.5 mg/kg iv atropine. Control heart rates for the normotensive and hypertensive dogs were not different (91 +/- 4 and 93 +/- 7 beats/min, respectively). Before autonomic blockade, the responses of normotensive and hypertensive dogs to nitroglycerin were not different. However, prolongation of the heart interval in response to phenylephrine in hypertensive dogs was significantly less than in normotensive dogs. In both groups, atropine nearly abolished the decrease in heart interval in response to nitroglycerin and the increase in heart interval in response to phenylephrine, although there were small but significant residual responses. Propranolol was without significant effect on heart interval responses to nitroglycerin and phenylephrine. We conclude that the baroreflex control of heart interval during transient decreases in arterial pressure is preserved in hypertensive dogs and is mediated mainly by decreases in parasympathetic outflow to the heart. In contrast, baroreflex control of heart interval during transient increases in arterial pressure is impaired in hypertension and is mediated mainly by activation of parasympathetic cholinergic mechanisms.

Animals↗
PubMed1981

Interaction between carotid and cardiopulmonary baroreflexes in control of plasma ADH.

The purpose of this study was to determine if there is an interaction between carotid baroreceptors (CBR) and cardiopulmonary receptors with vagal afferents (CPVA) in the control of plasma vasopressin (ADH). Changes in ADH (radioimmunoassay) in the superior vena cava were determined in 13 chloralose-anesthetized dogs with aortic nerves sectioned during concomitantly induced changes in CBR and CPVA input. CBR input was changed by altering pressure (CSP) in the isolated perfused sinuses. Carotid sinus pressure (CSP) was initially set at 50 mmHg. The CPVA input was reversibly interrupted by cooling the vagi to 0 degrees C while CSP was concomitantly increased to 135 or 200 mmHg or was held constant at 50 mmHg. Vagal cold block (VCB) with CSP held constant at 50 mmHg resulted in large increases in arterial pressure and plasma vasopressin. Increases in CSP to 200 mmHg resulted in significant decreases in arterial pressure and in plasma vasopressin despite concomitant VCB. VCB and concomitant increase in CSP to 135 mmHg resulted in a significant fall in arterial pressure, whereas plasma vasopressin tended to increase. Thus, the influence on arterial pressure of raising CSP to 135 mmHg exceeds that of VCB. In contrast, the influence of VCB on ADH equals or exceeds that of raising CSP to 135 mmHg. These differential responses of arterial pressure and plasma ADH suggest an interaction between CBR and CPVA in the control of ADH and arterial pressure.

Afferent Pathways↗
PubMed1981

The cardiocardiac sympathetic reflex during coronary occlusion in anesthetized dogs.

Cardiac sympathetic afferent fibers activated during coronary occlusion exert an excitatory influence on sympathetic discharge to the heart in cats after spinal cord section. The significance of this cardiocardiac sympathetic reflex response during myocardial ischemia in animals with an intact neuraxis is unknown. We studied the responses of efferent cardiac sympathetic nerve activity (CSNA), arterial pressure, and heart rate to coronary occlusion in two groups of dogs with cardiac sympathetic reflexes intact and with other reflex inputs affecting CSNA sectioned or controlled. In group I (n = 10), the vagi were sectioned, the spinal cord remained intact, and the carotid sinuses were isolated and perfused to maintain baroreceptor input constant. Coronary occlusion was performed at moderate and low basal levels of CSNA by setting carotid sinus pressure at 125-150 and 200 mm Hg, respectively. Under these conditions, CSNA was not altered by occlusion of either the anterior descending or the circumflex coronary artery. In group II (n = 4), the vagi were sectioned and the spinal cord was interrupted. In these dogs, CSNA increased significantly (61 +/- 19%) during coronary occlusion. These results show that an excitatory cardiocardiac sympathetic reflex can be demonstrated in dogs with spinal cords sectioned but not with spinal cords intact. This finding is consistent with the view that inhibitory bulbospinal pathways minimize the influence of the spinal cardiocardiac sympathetic reflex during myocardial ischemia in anesthetized dogs.

Animals↗
PubMed1981

Beta-1 receptor mediation of renin secretion elicited by low-frequency renal nerve stimulation.

The purpose of this study was to determine if renin secretion resulting solely from low-frequency renal nerve stimulation (no change in renal blood flow or urinary sodium excretion) is mediated by activation of beta-1 (beta-1) or beta-2 (beta-2) adrenergic receptors. Beta-1 and beta-2 adrenergic receptor blockade were produced with atenolol and butoxamine, respectively. Low-frequency renal nerve stimulation (0.5 Hz) increased renin secretion without altering mean arterial pressure, renal blood flow, glomerular filtration rate or urinary sodium excretion. The increase in renin secretion in response to renal nerve stimulation was blocked by beta-1 blockade with intrarenal atenolol (2.0 micrograms/kg/min) infusion. This dose of atenolol reduced the renal vasodilator response to intrarenal isoproterenol by only 48%, thus indicating modest beta-2 receptor blockade. A lower dose of atenolol (30 micrograms/kg i.v.) markedly decreased the tachycardia in response to i.v. isoproterenol (2 micrograms) but had no effect on the renal vasodilator response to intrarenal isoproterenol injection (2 micrograms), thus indicating selective beta-1 blockade. This dose of atenolol abolished the increase in renin secretion during renal nerve stimulation. In contrast, beta-2 receptor blockade with butoxamine (20 micrograms/kg/min) did not alter the renin secretion response to renal nerve stimulation. This dose of butoxamine decreased the renal vasodilator response to intrarenal isoproterenol by 73%, thus demonstrating significant beta-2 receptor blockade. These results indicate the low-frequency renal nerve stimulation (0.5 Hz) increases renin secretion without altering renal hemodynamics or urinary sodium excretion. This neurally mediated renin secretion resulted from activation of beta-1 adrenergic receptors.

Animals↗
PubMed1980

Sensitization of cardiac receptors (vagal afferents) by intracoronary acetylstrophanthidin.

The purpose of this study was to determine if sensitization of cardiac receptors with acetylstrophanthidin augments the inhibition of renal nerve activity resulting from expansion of the blood volume or from coronary artery occlusion. Ten chloralose-anesthetized dogs with sinoaortic baroreceptor denervation were subjected to volume expansion with dextran in saline. Under control conditions, volume expansion resulted in decreases in renal nerve activity (% or control) that were inversely related to left atrial pressure (-13.0%/mmHg left atrial pressure). After intracoronary acetylstrophanthidin, volume expansion resulted in a significantly greater suppression of renal nerve activity (-20.6%/mmHg). Occlusion of the circumflex coronary artery in 19 dogs with carotid baroreceptor denervation resulted in a 29 +/- 5% (SE) reduction in renal nerve activity. After intracoronary acetylstrophanthidin, circumflex occlusion resulted in a significantly greater decrease in renal nerve activity (45 +/- 4%). Vagotomy abolished the decreases in renal nerve activity, which resulted from volume expansion and from circumflex coronary occlusion. These data show that volume expansion and coronary occlusion reflexly decrease renal nerve activity via cardiac afferent vagal endings. These reflex inhibitory influences are augmented after intracoronary acetylstrophanthidin. The results are consistent with the view that intracoronary acetylstrophanthidin sensitizes cardiac afferent vagal endings.

Afferent Pathways↗
PubMed1980

Stimulation of cardiac receptors with veratrum alkaloids inhibits ADH secretion.

The purpose of this study was to determine whether cardiac receptors that are stimulated by veratrum alkaloids exert an inhibitory influence on the secretion of vasopressin (ADH). In six chloralose-anesthetized dogs, injection of cryptenamine (2 microgram/kg) into the circumflex coronary artery resulted in a significant (P < 0.05) fall in arterial pressure (-45 +/- 5 mmHg). Despite this hypotension and the presence of intact arterial baroreflexes, there was no change in plasma ADH (measured in the superior vena cava). In eight dogs with sinoaortic baroreceptor denervation, hemorrhage of 10 ml/kg decreased arterial pressure 20 +/- 5 mmHg (P < 0.05) and increased plasma ADH from 14 +/- 5 to 38 +/- 13 microU/ml (P < 0.05). Intracoronary injection of cryptenamine (1 microgram/kg) decreased plasma ADH to 23 +/- 7 microU/ml during the 5 min immediately after cryptenamine injection and to 16 +/- 4 microU/ml 20 min after injection. In eight dogs with sinoaortic denervation, hemorrhage and injection of vehicle resulted in a progressive increase in plasma ADH over the same time period. Vagotomy abolished the inhibitory response to cryptenamine injection. These data show that stimulation of cardiac receptors with vagal afferents by intracoronary injection of a veratrum alkaloid inhibits ADH secretion. Activation of these receptors can prevent arterial baroreflex-induced increases in ADH.

Afferent Pathways↗
PubMed1980

Interaction of cardiopulmonary and somatic reflexes in humans.

Activation of cardiopulmonary receptors with vagal afferents results predominantly in reflex inhibition of efferent sympathetic activity, whereas activation of somatic receptors reflexly increases sympathetic activity to the heart and circulation. Previous studies in experimental animals indicate that there is an important interaction between these excitatory and inhibitory reflexes in the control of the renal circulation. The purpose of this study was to determine whether there is a similar interaction between somatic and cardiopulmonary reflexes in humans. The activity of the cardiopulmonary receptors was altered (reduced) with lower body negative pressure (-5 mm Hg), which causes a decrease in cardiac filling pressure and a small reflex increase in forearm vascular resistance without accompanying changes in arterial pressure. Activation of somatic receptors by isometric handgrip for 2 min at 10 and 20% of maximum voluntary contraction resulted in reflex vasoconstriction in the nonexercising arm. Lower body negative pressure at -5 mm Hg produced a threefold augmentation in the forearm vasoconstrictor response to isometric handgrip in the nonexercising arm. This increase in resistance was significantly greater (P < 0.05) than the algebraic sum of the increases in resistance resulting from lower body suction alone plus isometric handgrip alone. Furthermore, it occurred despite a greater rise in arterial pressure, which would be expected to decrease forearm vascular resistance through activation of arterial baroreceptors and through passive dilatation of forearm vessels. Thus, removal of the inhibitory influence of cardiopulmonary receptors by pooling blood in the lower extremities enhances the somatic reflex. These data suggest an interaction between cardiopulmonary and somatic reflexes in the control of forearm vascular resistance in man.

Adult↗
PubMed1979

Interaction of somatic and cardiopulmonary receptors in control of renal circulation.

The purpose of this study was to determine if there is an important interaction between somatic and cardipulmonary receptors in the control of vasomotor outflow to the kidney. This interaction was examined by determining the renal vasoconstrictor responses to afferent electrical stimulation (30 V, 1 ms, 20--40 Hz) of the sectioned sciatic nerve in 8 chloralose-anesthetized dogs with sinoaortic deafferentation. During isovolemia, sciatic stimulation resulted in significant increases in arterial pressure and heart rate, and in renal vasoconstriction. Volume expansion significantly attenuated and vagotomy significantly augmented the renal vasoconstrictor responses to sciatic stimulation. These interventions did not significantly influence the arterial pressure or heart rate responses to sciatic stimulation. In 4 dogs with aortic nerves sectioned and carotid sinuses isolated and perfused at constant pressure (135 mmHg), the renal vasoconstrictor responses to stimulation were attenuated by volume expansion and augmented by vagotomy. These data show that in the absence of the arterial baroreceptors or with intermediate levels of carotid baroreceptor activation, volume expansion and, thus, augementation of discharge of cardiopulmonary receptors (vagal afferents) markedly attenuated the renal vasoconstrictor responses to somatic afferent stimulation.

Animals↗
PubMed1979

Acetylstrophanthidin-induced reflex inhibition of canine renal sympathetic nerve activity mediated by cardiac receptors with vagal afferents.

The present experiments were performed to determine whether digitalis-induced augmentation of cardiac receptor discharge could induce reflex reductions in renal sympathetic nerve activity. Intracoronary injection or epicardial application of acetylstrophanthidin (AS) in chloraloseanesthetized dogs caused large decreases in renal sympathetic nerve activity which were accompanied by modest decreases in heart rate and arterial pressure. Vagotomy prevented these reflex responses. Cholinergic blockade with atropine markedly attenuated the heart rate responses to AS but had little effect on the arterial pressure or renal nerve activity responses. Epicardial application of lidocaine blocked cardiac vagal afferents and the reflex responses to intracoronary AS. In sinoaortic denervated dogs, the relationships between doses of AS and mean arterial pressure, heart rate, and renal nerve activity responses were linear. Decreases in renal nerve activity were evoked by doses of AS which did not reflexly change heart rate or arterial pressure. These data show that AS can evoke reflex bradycardia, hypotension, and withdrawal of renal sympathetic nerve activity solely by augmenting the inhibitory influence of cardiac receptors with vagal afferents. This reflex effect may contribute to the changes in renal function and thus to the diuresis that occurs when heart failure is treated with digitalis.

Animals↗