Biomedical subjects

R L Malvin

Publications and source records attributed to R L Malvin.

At least 37 records · Page 2Linked to original sources

PubMed1988

Dopaminergic modulation of some central actions of angiotensin II in vivo.

Studies were performed in 12 conscious sheep of both sexes to determine if a brain dopaminergic pathway is involved in modulating the central actions of angiotensin II (Ang II) in regulating body temperature and plasma renin activity (PRA). Previous data showed that intracerebroventricular (ICV) infusion of Ang II significantly decreased PRA and body temperature. In contrast, converting enzyme inhibitor SQ 20881 (SQ) or dopamine (DA) significantly increased PRA and body temperature of sheep. In the present study, ICV infusion of the DA antagonist metoclopramide (MCP) (20 micrograms/min) significantly decreased PRA to 68 +/- 5% of the basal level. When sheep were pretreated with ICV MCP (20 micrograms/min) for 2 hr and then infused ICV with MCP (20 micrograms/min) plus DA (20 micrograms/min), Ang II (25 ng/min), or SQ (1 microgram/min), the PRA and temperature responses to DA, Ang II, or SQ were all abolished or attenuated significantly. The converse did not hold. Sheep pretreated with SQ (1 microgram/min) still showed a significant increase in body temperature (0.43 +/- 0.05 degree C) when infused with DA (20 micrograms/min). These results support the hypothesis that a central DA pathway is involved in the modulation of the actions of centrally administered Ang II on temperature and PRA.

Angiotensin II↗

PubMed1987

Natriuretic response to homologous heart extract in aglomerular toadfish.

Although the renal effects of the atrial natriuretic factor (ANF) have been widely investigated, the mechanism of its natriuretic and diuretic effect is still controversial. The purpose of this study was to investigate whether ANF has a specific tubular action distinct from any renal or systemic hemodynamic effects. Renal responses to homologous heart extract (HE) or synthetic ANF were examined in the aglomerular toadfish. A significant natriuresis and diuresis were observed following an intra-arterial injection of either HE (amount derived from 1 heart) or ANF (atriopeptin III, 20 micrograms). However, neither affected urinary excretion of K+. Synthetic ANF did not alter the excretion of Mg2+ or Ca2+. In addition HE showed a hypotensive effect, and ANF did not alter the mean arterial pressure significantly. Neither HE nor ANF affected heart rate. Injection of skeletal muscle extract or saline vehicle alone was without effect on renal function, mean arterial pressure, or heart rate. These results support the hypothesis that ANF has a specific tubular action to increase urinary Na+ and water excretion. The presence of a natriuretic factor was demonstrated in the heart of the fish.

Animals↗

PubMed1987

Centrally administered atrial natriuretic factor increases renal water excretion.

The effects of intracerebroventricular (ICV) infusion of atrial natriuretic factor (ANF; atriopeptin III) on renal function, plasma concentrations of antidiurectic hormone, aldosterone, and plasma renin activity (PRA) were examined in anesthetized rats and sodium-depleted conscious sheep. The results were compared with those obtained by intravenous infusion of the same dose of ANF. In both rats and sheep, urine volume was increased four- to sixfold over basal values by ICV infusion of ANF. The response was not associated with increased excretion of sodium or potassium. However, urine osmolality was decreased, and free water clearance increased. Intravenous infusion of the same dose of ANF was without effect. Neither mean arterial blood pressure nor heart rate was changed by the ICV infusion of ANF. In the sheep, renal plasma flow showed no significant changes and glomerular filtration rate was unaltered with the exception of a single experimental period out of four periods of ICV ANF infusion. Plasma concentration of ADH was decreased and PRA increased, whereas aldosterone levels remained unchanged as a function of ICV ANF. In the rat, the diuretic response to ANF was prevented by continuous intravenous infusion of a subpressor dose of ADH. These results suggest that ANF within the central nervous system inhibits secretion of ADH.

Aldosterone↗

PubMed1987

Temperature sensitivity of renin-angiotensin system in the ground squirrel.

The alteration of renin release by alpha- and beta-adrenoceptors located on the juxtaglomerular cells has been shown to be temperature sensitive in nonhibernating mammals. These experiments investigate the effects of temperature on renin secretion by cortical slices of kidneys from the thirteen-lined ground squirrel Spermophilus tridecemlineatus. At 37 degrees C, beta-stimulation (isoproterenol 10(-7) M) increased the release of renin by slices taken from nonhibernating ground squirrels but had no effect on those taken from hibernating squirrels. The alpha-agonist phenylephrine (10(-5) M) had no effect on slices from nonhibernating squirrels but enhanced the release rate in those from hibernating ground squirrels, providing the first evidence of in vitro stimulation of renin release by an alpha-agonist. When incubated at 11 degrees C, kidney slices from both hibernating and nonhibernating animals were unresponsive to both alpha- and beta-agonists until incubation times were doubled. Under these prolonged conditions, phenylephrine again stimulated renin release. These results indicate that both in vitro and in vivo cooling alter the responses of alpha- and beta-adrenoceptors to renin-releasing stimuli.

Angiotensin II↗

PubMed1987

Central dopaminergic regulation of aldosterone secretion in sheep.

Central dopaminergic mechanisms involved in the regulation of plasma aldosterone concentration were investigated in 16 conscious sheep following Na depletion with intramuscularly administered furosemide. Intracerebroventricular infusion of dopamine (20 micrograms/min) decreased plasma aldosterone significantly to 52 +/- 8% of basal level and increased plasma renin activity (PRA) significantly to 172 +/- 25% of basal level in this animal model. In addition, intracerebroventricular infusion of the dopamine antagonist metoclopramide (20 micrograms/min) in artificial cerebrospinal fluid vehicle significantly increased aldosterone levels to 144 +/- 14% of basal level and decreased PRA to 62 +/- 5% of basal value. Neither intracerebroventricular infusion of the vehicle nor intravenous infusions of metoclopramide or dopamine at the same doses changed aldosterone or PRA levels. Intracerebroventricular bolus injections of metoclopramide (20 micrograms/kg in 0.4 ml of vehicle) were also effective, increasing aldosterone levels to 266 +/- 22% of basal level and decreasing PRA to 70 +/- 12% of basal level. Intravenous bolus injections of the same dose of metoclopramide were ineffective. Dopamine was infused intracerebroventricularly into two uniadrenalectomized sheep with the remaining adrenal transplanted to the neck. Aldosterone levels were decreased to 49 +/- 10% of basal level, and PRA was increased to 157 +/- 10% of basal value. None of the infusions or injections changed arterial or intracranial pressure, or plasma K, Na, and cortisol levels. These data indicate that endogenous or exogenous dopamine may act on central dopamine receptors to decrease plasma aldosterone concentration by an unknown humoral mechanism. The known aldosterone regulators, plasma Na, K, angiotensin II, and adrenocorticotropic hormone, are not involved in the regulation.

Adrenal Glands↗

PubMed1987

Atrial natriuretic factor inhibits vasopressin secretion in conscious sheep.

To test the hypothesis that atrial natriuretic factor (ANF) has a centrally mediated action on body fluid homeostasis, the effects of intracerebroventricularly (ICV) infused ANF on plasma vasopressin (AVP) concentration and urinary water and electrolyte excretion were investigated in euhydrated and water-deprived conscious sheep. ICV ANF decreased plasma AVP concentration and increased urinary free water excretion in euhydrated sheep, with excretion of Na and K unaltered. However, ICV ANF did not affect urinary volume, free water clearance, or excretion of Na and K in dehydrated animals, although plasma AVP concentration was significantly decreased. The relationship between urine volume and plasma AVP concentration was fitted by a power curve: urine volume = 0.79 X [AVP]-0.71; urine volume changes very little as a function of AVP concentration at the higher ranges. Intravenous infusion of the same amount of ANF was without effect on plasma AVP concentration or urinary excretion in both euhydrated and dehydrated animals. Mean arterial pressure was unchanged throughout all experiments. These results are consistent with the hypothesis that central ANF inhibits AVP secretion.

Animals↗

PubMed1986

Central 6-hydroxydopamine and renal sodium retention in mineralocorticoid-treated rats.

Cerebroventricular administration of 6-hydroxydopamine attenuated the development of deoxycorticosterone hypertension in the rat but did not affect the initial period of renal sodium retention. However, escape from the sodium retention was greater in 6-hydroxydopamine-treated rats. These data support the hypothesis that destruction of central catecholamine-containing neurons influences the renal handling of sodium. The enhanced escape may lead to diminished total body sodium, which attenuates the development of deoxycorticosterone hypertension.

Animals↗

PubMed1986

Different production and decay rates of six renin forms isolated from rat plasma.

Rat kidney contains six forms of renin, which are in different proportion from those found in plasma. We tested the hypothesis that differential removal and production of the forms might explain the differences between stored and circulating renins. In one group of rats, the six forms of renin were measured in plasma, 10 min after hemorrhage, or after aortic constriction. Plasma was run on an isoelectric focusing gel, and the six peaks of renin activity were expressed either as angiotensin I per hour per milliliter or as a percentage of the total plasma renin concentration. After hemorrhage or aortic constriction, the concentration of each form was significantly increased; the profile of circulating renin was significantly modified, showing an increase in proportion of form 2 and a decrease of forms 4, 5, and 6. In a second group, the disappearance of each form was measured 0 to 100 min after nephrectomy and fitted a two-exponential decay curve. Interpreted as a two-pool system with degradation from pool 1, the degradation rate decreased progressively, going from form 1 to 6. In a third group, arterial and renal venous blood were collected. The profile of secreted renin was calculated from the arterial venous difference. This profile fitted the prediction of the two-compartment model. Our data support the hypothesis that the proportion of each circulating renin form is the result of a balance between the rate of production of renin of constant composition and the degradation of the six forms at different rates.

Animals↗

PubMed1986

Renin heterogeneity in stroke-prone hypertensive and normotensive rats.

Six forms of renin are found in the rat kidney. We studied their secretion in renal slices from spontaneously hypertensive stroke-prone rats (SHRSP) and Wistar-Kyoto rats (WKY). Incubation media from renal slices were subjected to isoelectric focusing. Six peaks of renin activity with different isoelectric points were found. The renin concentration of each form was expressed as a percentage of the total recovered from the gel. We established that the forms secreted by renal slices of SHRSP differed from those of WKY: SHRSP slices released a higher proportion of forms focusing at the more acidic pH. The distribution of the six renin forms and of blood pressure (BP) among animals of the F1, F2, and backcross progenies resulting from the cross of SHRSP and WKY rats were studied. In the F1, BP, percentage of renin form 2, and a combination of the percentage of forms 4 + 5 + 6 were intermediate between the parental lines. The backcross rats showed BP and percentages of forms closer to their SHRSP or WKY parent. In the F2, the distribution of BP, percentage of forms 2 and 4 + 5 + 6 take the form of a unimodal distribution with a significantly larger variance than F1. The increase in the correlation between percentage of renin forms and BP, and between renin concentration of BP, in the segregating progenies over that observed in the parental lines and the F1, are support for the hypothesis that these traits are under the control of common genetic mechanisms.

Animals↗

PubMed1986

Angiotensin-stimulated drinking in marine fish.

Drinking rates in both marine and freshwater stenohaline fish were studied by measuring the ingestion of polyethylene glycol that had been added to the aquarium water. Two marine species, the long-horned sculpin and the flounder, and three freshwater species, the common goldfish, the mottled sculpin, and the common shiner, were used. Control drinking rates in freshwater fish averaged 0.03-0.1% body wt/h and in marine fish varied between 0.06 and 0.24% body wt/h. Intramuscular injections of angiotensin II (ANG II) stimulated drinking two- to threefold in the two marine species but had no effect on the drinking rate of the freshwater species. Hemorrhage (1-2% of body wt) also stimulated drinking in the two marine species (6- to 10-fold) but did not affect the drinking rate of two freshwater species. Thus exogenous ANG II and hemorrhage stimulate drinking in two marine stenohaline fish as they do in mammals. These responses were absent in the three freshwater fishes studied. However, injection of converting enzyme inhibitor (SQ 20881) or saralasin in order to block endogenous ANG II did not attenuate either basal or hemorrhage-stimulated drinking in the marine fish.

Angiotensin II↗

PubMed1986

Changes of renin isoelectric heterogeneity after acute and chronic stimulation of renin secretion.

Changes in the multiple forms of renin secreted or stored in vitro by renal cortical slices were studied in rats made hypertensive with deoxycorticosterone, adrenalectomized rats, and rats fed a high or low salt diet. Renal slices from normal rats were also incubated with angiotensin II, vasopressin, and verapamil. Aliquots of incubation media were subjected to isoelectric focusing, and the six forms of renin were quantified and expressed as a percentage of the total renin activity recovered from the gel. The results showed that chronic and acute stimulation of renin secretion produced a similar modification of the isoelectric focusing profile, consisting of an increased proportion of renin forms with the more acidic isoelectric points. The change in the proportions of the more acidic renin forms was greater with chronic stimulation than that after stimulation with verapamil. However, chronic and acute inhibition or reductions of the rate of renin secretion did not modify the renin profile. We suggest that the progression in the shift of secreted renin forms to those with the more acidic isoelectric points correlates with the intensity or duration of stimulation of renin secretion. These data support the hypothesis that different pools of renin exist and are altered differently by chronic and acute stimulation of renin secretion.

Adrenalectomy↗

PubMed1985

Lack of renal effects of DOCA, ACTH, spironolactone, and angiotensin II in Squalus acanthias.

Angiotensin II was infused intravenously in spiny dogfish sharks (Squalus acanthias). There were no significant effects on arterial blood pressure, glomerular filtration rate, urine flow, or Na excretion either in comparison with pre- and postinfusion values or in comparison with values measured in a control group of fish given elasmobranch saline intravenously. In other dogfish, glomerular filtration rate, urine flow, and Na and K excretory rates were measured for 3 days following implantation of desoxycorticosterone (DOCA), adrenocorticotropin (ACTH), or spironolactone; a control group was given no drug. There were no significant differences between these four groups of fish with respect to any of the measured parameters. These results suggest that the dogfish kidney is not a target organ for several substances known to affect renal function, either directly or indirectly, in other animals.

Adrenocorticotropic Hormone↗

PubMed1985

Modification of renin isoelectric heterogeneity in Goldblatt hypertensive rat.

Six forms of renin have been described in rat kidney. Different stimuli resulted in secretion of unique profiles of those forms. We studied their storage and secretion in the two-kidney, one-clip Goldblatt hypertensive rat (GHR). Renal venous blood, kidney homogenates, and incubation media from cortical slices were subjected to isoelectric focusing. In all samples tested, six peaks of renin activity were found with isoelectric points at pH 5.90, 5.70, 5.40, 5.20, 5.00, and 4.80. The quantity of renin activity for each form was expressed as a percentage of the total recovered from the gel. In control kidneys the profile of renin stored and that released by in vitro slices were similar. However, in plasma, the percentage of renin focusing at the more basic pH was decreased. This is in agreement with other work showing that the liver removes the more basic forms more rapidly than the acidic forms. The clipped kidney of GHR secreted, both in vivo and in vitro, a profile of renin forms that was significantly different from the control kidney. The difference was expressed by an increase in the secretion of the more acidic forms by the clipped kidney. It is hypothesized that changes in the secretory profile of renin may reflect changes in storage and synthesis of those forms.

Animals↗

PubMed1985

Thermal responses to central angiotensin II, SQ 20881, and dopamine infusions in sheep.

The thermoregulatory role of brain angiotensin II (ANG II) was tested by intracerebroventricular (IVT) infusion of ANG II or the converting enzyme inhibitor SQ 20881 (SQ) in 15 conscious sheep. Deep body temperature decreased 0.30 +/- 0.07 degree C (SE) during the 3-h period of IVT ANG II (25 ng/min) infusion (P less than 0.05) and increased 0.50 +/- 0.13 degree C during IVT SQ (1 microgram/min) infusion (P less than 0.01). To determine whether the rise in body temperature after IVT SQ infusion might be the result of a central renin-angiotensin system (RAS), SQ was infused IVT in five conscious sheep 20 h after bilateral nephrectomy. This resulted in a significant rise in body temperature of 0.28 +/- 0.05 degree C (P less than 0.05). When vasopressin antidiuretic hormone (ADH) was infused intravenously at the same time of IVT SQ infusion, the rise in temperature was depressed, but ADH did not lower the temperature below basal. IVT dopamine (20 micrograms/min) increased body temperature by 0.40 +/- 0.04 degree C (P less than 0.01), which was qualitatively similar to the result with IVT SQ. These data support the hypothesis that endogenous brain ANG II may play a role in thermoregulation. Furthermore, plasma ADH level, regulated in part by brain ANG II, is probably not the mediator of that thermoregulation. The similar effects of IVT dopamine and SQ on body temperature strengthen the hypothesis that dopamine may be involved in the central action of brain ANG II.

Angiotensin II↗

PubMed1985

Central effects of angiotensin II and dopamine in sodium-depleted sheep.

The effects of intracerebroventricular (IVT) infusion of angiotensin II (ANG II), the converting enzyme inhibitor SQ 20881, and dopamine were studied in 15 conscious Na-depleted sheep. IVT ANG II (25 ng/min) significantly increased plasma aldosterone (163 +/- 24%) and vasopressin (ADH) (533 +/- 100%). Plasma renin activity (PRA) was decreased to 64 +/- 10% of basal. IVT SQ (1 microgram/min) decreased aldosterone to 70 +/- 10% and ADH to 55 +/- 9% of basal. PRA increased to 124 +/- 10%. There were no significant changes in plasma Na, K, or cortisol levels nor in mean arterial or intracranial pressure after either infusion. Increasing the dose of SQ to 10 micrograms/min resulted in an increased magnitude of change in the same variables. IVT SQ (1 microgram/min) significantly decreased aldosterone level in five nephrectomized sheep. The responses to IVT dopamine (20 micrograms/min) were qualitatively similar to those elicited by IVT SQ. These data support the existence of an endogenous brain renin-angiotensin system (RAS) independent of the renal RAS. ANG II acts centrally to regulate plasma ADH, aldosterone, and PRA levels. The similarity of the responses to SQ and dopamine suggests that a dopaminergic pathway may be involved in these responses.

Aldosterone↗

PubMed1985

Differential secretion and removal of multiple renin forms.

Hepatic clearance of renin in anesthetized dogs was measured during aortic constriction and after nephrectomy. Aortic constriction caused a transient increase in the hepatic extraction ratio for renin (ER) from 0.34 +/- 0.05 to 0.52 +/- 0.05, whereas nephrectomy caused the ER to decrease with time. Isoelectric focusing of plasma samples over an average pH gradient of 4.0-6.2 yielded several peaks of renin activity. Peaks focusing above pH 5.0 were combined and arbitrarily classified as basic renin, whereas peaks below pH 5.0 were classified as acidic renin. In each period the ER for basic renin was significantly greater than that for acidic renin. The proportion of basic renin was transiently increased at 10 min (59 +/- 4%) compared with control (41 +/- 4%). This contributed to the increased ER after constriction. The decreased ER after nephrectomy, however, was not solely due to differential removal of these forms. We conclude that hepatic clearance of renin is partly a function of the type of renin secreted by the kidney, which in turn may change with the duration of the secretory stimulus.

Animals↗

PubMed1985

Atrial extracts increase glomerular filtration rate in vivo.

We measured the effect of a constant infusion of rat atrial extract on the glomerular filtration rate (GFR), renal plasma flow (RPF), and plasma renin concentration (PRC) of bioassay rats. The infusion rate of the atrial extract was 0.038 ml/min, which represented 1.25 mg of homogenized atrial tissue/min. To ensure that dead space was cleared, clearance measurements during the atrial extract infusion were not begun until urine flow had increased and 300 microliter of urine had been excreted. In the first series of rats, control GFR was 0.69 +/- 0.05, increased to 1.04 +/- 0.06 during infusion of atrial extract, and then decreased to 0.72 +/- 0.08 ml X min-1 X 100 g-1 during the recovery period. In a second series, RPF was also measured. GFR increased from 0.92 +/- 0.02 to 1.15 +/- 0.05 ml X min-1 X 100 g-1, while RPF was unchanged. In both series, the increase in GFR was statistically significant. Constant infusion of atrial extracts had no significant effect on PRC. These studies provide evidence that an atrial factor can cause a large increase in GFR, which may contribute to the natriuretic effect of atrial extracts.

Animals↗

PubMed1985

Role of natriuretic factor in central nervous system (CNS)-induced natriuresis.

The presence of a natriuretic factor in the plasma of rats in which a 350 mM Na (high Na) artificial cerebrospinal fluid (CSF) was infused into the lateral ventricle was tested. Blood was obtained from control rats and rats which received an infusion of high Na CSF intraventricular (IVT) for 15 min. The plasma was incubated for 30 min at room temperature, acidified, placed in a boiling-water bath, and then centrifuged. The plasma supernate was assayed for natriuretic activity in pentobarbital anesthetized bioassay rats. Sodium excretion increased 6.5 +/- 1.1 mueq/kg X min in rats which received an infusion of a control saline solution, 13.3 +/- 3.2 mueq/kg X min in rats which received infusion of control plasma supernates, and 32.1 +/- 8.3 mueq/kg X min in those rats which received plasma supernates from rats infused with high Na CSF IVT. Blood pressure was unchanged in all groups. The increment in sodium excretion elicited by plasma supernate from the high Na IVT group was significantly greater than that elicited by either control saline solution or control plasma extracts. Therefore, it is concluded that a heat-stable and nonpressor natriuretic factor is present in the plasma of rats infused IVT with high Na CSF.

Animals↗