Biomedical subjects

M Gellai

Publications and source records attributed to M Gellai.

At least 55 records · Page 3Linked to original sources

PubMed1990

Hemodynamic responses to leukotriene receptor stimulation in conscious rats.

We evaluated the effects of leukotrienes (LTs) C4 and D4 on systemic and renal hemodynamics in conscious rats. Intravenous injections of LTC4 or LTD4 (0.5-10 micrograms/kg) caused dose-dependent decreases in cardiac output (CO), renal blood flow (RBF), and heart rate (HR). Flow alterations were accompanied by increased systemic and renal vascular resistances (SVR and RVR) and mean arterial blood pressure (MAP). No secondary hypotensive effect was observed. The HR response was biphasic, with tachycardia replacing the initial brief bradycardia. The changes in RBF and CO were not concurrent; the maximum RBF decrease (47.6 +/- 9.5%, P less than 0.05) occurred when CO was down only by 9.1 +/- 3.6% (P less than 0.05) and RBF had fully recovered in 3-4 min, while CO was still down by 26.3 +/- 3.5% (P less than 0.001). Hematocrit (HCT) increased after the injection of 5 and 10 micrograms/kg doses of LTC4 or LTD4, and its time course of recovery to basal level (30-60 min) paralleled that of CO. Sustained intravenous infusion of the selective LT receptor antagonist, SK&F 104353, dose-dependently inhibited the immediate hemodynamic changes after LTD4 injections. SK&F 104353 also attenuated the increase in vascular permeability and the prolonged decrease in CO, suggesting that the observed cardiac and vascular effects of LTs were mediated by stimulation of LT receptors.

Animals↗

PubMed1990

Modulation of vasopressin antidiuretic action by renal alpha 2-adrenoceptors.

It has been almost 40 years since the diuretic effect of alpha-adrenoceptor agonists was first demonstrated. Two possible mechanisms were proposed: inhibition of vasopressin secretion and antagonism of the cellular hydrosmotic actions of vasopressin. The debate could not be settled then for the lack of appropriate experimental models and pharmacological tools. Advances made in adrenoceptor pharmacology in the 1970s such as 1) subdivision of alpha-adrenoceptors into alpha 1- and alpha 2-subtypes; 2) development of selective agonists and antagonists; and 3) localization of both adrenoceptor subtypes in the kidney, including the proximal and collecting tubules, stimulated new research. With regard to renal adrenoceptors, selective alpha 2-agonists have been shown to induce diuresis in dogs and rats. Whereas in the dog the increase in urine flow results mostly from an increase in osmolal clearance, in the rat the diuresis results in large part from an increase in the excretion of solute-free water. In vitro studies on isolated collecting tubules from rats and rabbits (none from dogs) have shown that alpha 2-agonists inhibit vasopressin-induced adenosine 3',5'-cyclic monophosphate formation and that this effect is mediated by the inhibitory guanine nucleotide regulatory protein and abolished by pertussis toxin treatment. In vivo evidence in support of such a mechanism was presented from conscious Brattleboro homozygous rats in which a selective alpha 2-agonist inhibited the antidiuretic effect of exogenous vasopressin, and this effect was abolished by pertussis toxin. The physiological importance of renal alpha 2-adrenoceptors was identified by use of adrenal medullectomized rats and the alpha 2-antagonist, yohimbine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Effect of dopamine beta-hydroxylase inhibition on systemic hemodynamics in conscious, spontaneously hypertensive rats.

The acute and chronic effects of a potent and selective dopamine beta-hydroxylase inhibitor, SK&F 102698 [1-(3,5-difluorobenzyl)imidazole-2-thiol], on systemic hemodynamic variables were assessed in chronically instrumented spontaneously hypertensive and normotensive Wistar rats. The changes observed in the hypertensive rats were compared with those obtained by vehicle in a different group of rats. Following intragastric administration of SK&F 102698 (75 mg/kg), blood pressure and cardiac output decreased gradually in both strains of rats, while total peripheral vascular resistance remained unchanged. The antihypertensive effect of repeated daily administration of SK&F 102698 in the hypertensive rats was sustained for the duration of treatment. During the acute phase, the decrease in cardiac output was due to bradycardia. In addition, as a result of hemodynamic changes, SK&F 102698 significantly reduced the minute work output of the heart. The results indicate that SK&F 102698 lowers blood pressure primarily by decreasing cardiac output.

Animals↗

PubMed1990

Effect of carvedilol on renal hemodynamics and renal excretory function in spontaneously hypertensive rats.

The effects of the novel antihypertensive agent, carvedilol, on renal hemodynamics and excretory function have been investigated and compared with the effects of labetalol in conscious, spontaneously hypertensive rats. Sustained intravenous infusion of carvedilol or labetalol at a rate of 10 micrograms/kg/min resulted in a significant decrease in blood pressure which was equivalent in magnitude for both drugs. Carvedilol had no effect on renal hemodynamic parameters; glomerular filtration rate, renal blood flow, and filtration fraction were unchanged. In contrast, labetalol decreased the glomerular filtration rate by 13% (p less than 0.01) and the filtration fraction was reduced from 28 to 24%. Inasmuch as renal blood flow was unchanged and perfusion pressure was reduced, both compounds decreased renal vascular resistance. Urine flow decreased and osmolality increased with both carvedilol and labetalol. However, excretion of electrolytes was affected differently with the two compounds. While sodium and potassium excretion were significantly decreased with labetalol, sodium and potassium excretion remained stable during carvedilol infusion, which represents an important beneficial effect for a potent systemic vasodilator. We conclude, therefore, that carvedilol does not compromise the renal autoregulatory integrity in hypertensive rats, and that the antihypertensive activity of the compound is associated with an apparent 'renal sparing' effect, in that the decrease in blood pressure does not compromise the urinary excretion of sodium.

Animals↗

PubMed1989

Noncyclic vasopressin analogs are effective diuretics in conscious rats.

Linear vasopressin analogs lacking a cyclic hexapeptide ring have recently been reported to possess vasopressin antagonist activity. In conscious, chronically catheterized, euhydrated Sprague-Dawley rats, we have compared the effects of two noncyclic vasopressin analogs, peptide 1 ([1-admantaneacetic acid,2-(O-ethyl)-D-tyr,4-val,6-(2-aminobutyric acid),9-arg]arginine vasopressin) and peptide 2 ([1-propionic acid, 2-(O-ethyl)-D-tyr,4-val,6-(2-aminobutyric acid),9- arg]arginine vasopressin), with a cyclic arginine vasopressin antagonist (SK&F 105494; [1-des cysteine, cyclo(2-O-ethyl-D-tyrosine,6-L-(2-amino-6,6-cyclopentamethylene suberic acid], 4-valine,7-arginine,8-D-arginine, 9-des glycine]-vasopressin). All three analogs caused a dose-dependent increase in urine flow by increasing free-water clearance without significantly changing osmotic clearance or sodium excretion, indicating true functional vasopressin antagonism. Peptides 1 and 2 were as efficacious in inducing a diuresis as SK&F 105494. The order of diuretic potency among the three analogs in vivo was the same as the order of potency determined by in vitro binding to rat renal membrane homogenates, suggesting that the analogs exerted their diuretic effect by acting at renal vasopressin receptors. Thus, noncyclic vasopressin analogs, which are easier to synthesize then cyclic structures, could provide new strategies in the design of drugs for the treatment of water balance disorders.

Animals↗

PubMed1988

Mechanism of alpha 2-adrenoceptor agonist-induced diuresis.

In vivo and in vitro studies were performed to assess the mechanism of the diuretic effect of B-HT 933, a selective alpha 2-adrenoceptor agonist. In conscious Sprague-Dawley rats whose plasma vasopressin (AVP) levels were increased by infusion of hypertonic NaCl, B-HT 933 had no effect on AVP secretion. In Brattleboro homozygous (DI) rats, the antidiuretic dose response to AVP was shifted to the right by B-HT 933. In addition, a sustained antidiuresis induced in rats by infusion of 10 pg/min AVP was attenuated by B-HT 933 in a concentration-dependent manner. Pretreatment of DI rats with pertussis toxin (2 micrograms/kg iv) 4-5 days before testing abolished the inhibitory effect of B-HT 933 on AVP-induced antidiuresis. In outer medullary collecting ducts of DI rats, norepinephrine and B-HT 933 produced significant inhibition of AVP-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) accumulation. In contrast, the selective alpha 1-adrenoceptor agonist cirazoline had no effect on AVP-induced cAMP formation. The inhibitory effect of norepinephrine was antagonized by the selective alpha 2-adrenoceptor antagonist rauwolscine but not by prazosin, a selective alpha 1-antagonist. In outer medullary collecting ducts dissected from the pertussis toxin-treated DI rats used in the in vivo studies, the inhibitory effect of norepinephrine and B-HT 933 on AVP-stimulated cAMP accumulation was abolished. The results indicate that the hydrosmotic action of AVP is inhibited by alpha 2-agonists via a pertussis toxin-sensitive mechanism.

Adrenergic alpha-Agonists↗

PubMed1988

Oxytocin induces a transient increase in cytosolic free [Ca2+] in renal tubular epithelial cells: evidence for oxytocin receptors on LLC-PK1 cells.

We examined the effects of oxytocin on renal tubular epithelial LLC-PK1 cells. In cells loaded with Fura 2, we found that 1 microM oxytocin induced a rapid increase in cytosolic free [Ca2+]i from 120 nM to 250 nM within 12 sec. [Ca2+]i then decreased and leveled at 148 nM. Calcium was mobilized from intra- and extra-cellular sources. Oxytocin-induced calcium mobilization was dose dependent (EC50 between 5 and 30 nM). Oxytocin also stimulated calcium efflux which was blocked by the selective oxytocin antagonist KB-5-21. Calcium mobilization was a likely consequence of enhanced phosphatidylinositol turnover, because oxytocin rapidly increased the formation of inositol phosphates including Ins1,4,5P3. Calcium transients were induced by oxytocin and the oxytocin selective analog AM-2-40 and blocked by the oxytocin-selective antagonist KB-5-21. Lysine vasopressin, the selective V2 agonist dDAVP, and the V1-selective agonist SK&F 105349 were at least 10- to 100-fold less potent than oxytocin and exhibited only partial agonist activity. Using peptide analogs, a poor correlation was found between antagonism of oxytocin-induced calcium transients of LLC-PK1 cells and pig kidney V2 and rat liver V1 receptor affinity. These data indicate that oxytocin-induced calcium transients in LLC-PK1 cells were not mediated by V1 or V2 vasopressin receptors, but by oxytocin receptors. However, the poor correlation between antagonism at the LLC-PK1 receptors and the rat uterus oxytocin receptors suggests marked differences in antagonist recognition. We have also identified specific, saturable, high affinity oxytocin-binding sites of low density on intact LLC-PK1 cells (KD = 1.9 nM; Bmax = 3.2 fmol/10(6) cells). The relative analog affinities for these binding sites correlated well with their effects on oxytocin-induced calcium transients. We conclude that in LLC-PK1 cells, oxytocin stimulates a transient rise in cytosolic free [Ca2+]i and the formation of inositol phosphates, including Ins1,4,5P3. The effects on [Ca2+]i probably are not mediated by V1 and V2 vasopressin receptors, but by putative oxytocin receptors.

Animals↗

PubMed1988

Inhibition of vasopressin-stimulated cyclic AMP accumulation by alpha-2 adrenoceptor agonists in isolated papillary collecting ducts.

The effects of selective alpha adrenoceptor agonists and antagonists on vasopressin (VP)-sensitive cyclic AMP (cAMP) formation in microdissected rat papillary collecting ducts were examined. In the presence of 10(-10) M VP, norepinephrine and the selective alpha-2 adrenoceptor agonist, B-HT 933, produced almost total inhibition of VP-stimulated cAMP accumulation. Half-maximal inhibition occurred at 1 x 10(-8) M and 6 x 10(-7) M for norepinephrine and B-HT 933, respectively. Cirazoline, a selective alpha-1 adrenoceptor agonist, had no significant effect on VP-stimulated cAMP accumulation. The inhibitory effects of norepinephrine and B-HT 933 were antagonized by rauwolscine but not by prazosin. The antagonism of B-HT 933-induced inhibition of VP-stimulated cAMP accumulation was competitive with an antagonist dissociation constant (KB) of 10.9 x 10(-9) M. Preincubation of papillary collecting ducts with pertussis toxin (1 microgram/ml for 1 hr at 37 degrees C) attenuated, by 65%, the inhibitory effect of B-HT 933 on VP-stimulated cAMP levels. These results demonstrate that alpha-2 adrenoceptors capable of inhibiting VP action are present on the papillary collecting duct. Furthermore, the alpha-2 adrenoceptor-induced inhibition of VP-stimulated cAMP accumulation is pertussis-toxin sensitive. This suggests that alpha-2 adrenoceptors are coupled negatively to adenylate cyclase, via the guanine nucleotide binding protein, in the collecting tubule.

Adenylate Cyclase Toxin↗

PubMed1987

Cardioinhibitory effect of atrial peptide in conscious rats.

The hemodynamic and renal excretory responses to 150-min atriopeptin II (AP II) infusion (330 ng X kg-1 X min-1) were assessed in five chronically instrumented rats with (FR protocol) and without (NR protocol) replaced urinary fluid losses. The observed changes were compared with those obtained by vehicle in the same rats. The hypotension seen with AP II infusion (120-min value: -27 +/- 2%, FR and NR responses combined) was due solely to a decreased cardiac output (CO; 120-min combined value: -34 +/- 3%). Total peripheral resistance remained unchanged or slightly elevated. A drop in stroke volume plus a later-developing (by 75-90 min) decrease in heart rate contributed to the CO decline. This latter bradycardic component, the opposite response to that typically produced reflexly by hypotension, was reversed by atropine sulfate treatment at 120 min and may thus be neural in origin. The finding of similar hemodynamic changes in the FR and NR rats and the lack of a significant effect of AP II on hematocrit suggest that volume depletion or a plasma extravasation were not contributors to the cardioinhibitory effect of the peptide.

Animals↗

PubMed1987

Localization of alpha 2-adrenoceptor-mediated increase in renal Na+, K+, and water excretion.

Free-flow micropuncture and clearance studies were conducted in male Sprague-Dawley rats to investigate the effects of alpha 2-adrenoceptor stimulation on Na+, K+, and water transport along the nephron. Intravenous infusion of the selective alpha 2-adrenoceptor agonist B-HT 933 at 1 mg X kg-1 X h-1 increased urinary flow rate from 16.2 +/- 3.6 to 84.8 +/- 11.9 microliter/min, fractional excretion of Na+ from 1.36 +/- 0.31 to 3.57 +/- 0.52%, and fractional excretion of K+ from 26.9 +/- 3.0 to 42.3 +/- 2.2%, The diuresis, saluresis, and kaliuresis were not the result of increases in glomerular filtration rate or mean arterial blood pressure. Urine osmolality decreased from 1,126 +/- 177 to 325 +/- 33 mosmol/kg water and in 8 of the 11 animals studied B-HT 933 decreased urine osmolality to hyposmotic levels, suggesting a possible interaction between the alpha 2-adrenoceptor agonist and vasopressin. The alpha 2-adrenoceptor antagonist yohimbine (0.25/mg bolus, iv) inhibited the diuresis, saliuresis, and kaliuresis. In micropuncture studies, B-HT 933 was without effect on single-nephron glomerular filtration rate or on Na+, K+, and water transport along the superficial proximal tubule, loop of Henle, or distal tubule. Thus stimulation of alpha 2-adrenoceptors increases Na+, K+, and water excretion by inhibiting tubule reabsorption of these substances at nephron sites beyond the superficial distal tubule, most likely by the collecting tubule.

Animals↗

PubMed1987

Renal effects of selective alpha-1 and alpha-2 adrenoceptor agonists in conscious, normotensive rats.

The effects of the selective alpha-1 adrenoceptor agonist, cirazoline, and the selective alpha-2 adrenoceptor agonist, B-HT 933, were assessed on renal hemodynamics and on water and solute excretion in conscious, chronically instrumented rats. Infusion (i.v.) of equipressor doses of cirazoline and B-HT 933, 0.04 and 4 mg/kg/hr, respectively, decreased renal plasma flow without changing glomerular filtration rate. Cirazoline infusion did not affect urinary excretion of water, electrolytes or total solutes. In marked contrast, B-HT 933 increased urine flow and sodium excretion significantly (P less than .01) but did not significantly alter potassium and urea excretion. Urine osmolality decreased to hyposmotic levels (from 613 +/- 86 to 172 +/- 8 mOsmol/kg of H2O) during the infusion of B-HT 933, suggesting a possible interaction between the alpha-2 adrenoceptor agonist and the vasopressin system. This diuretic action of the selective alpha-2 adrenoceptor agonist was also observed after the i.v. infusion of a subpressor dose (0.4 mg/kg/hr) of B-HT 933. In rats treated with the ganglionic blocker, hexamethonium (10 mg/kg i.v.), the B-HT 933-induced diuresis was not affected, confirming an action in the periphery, possibly at the level of the kidney. These results suggest that stimulation of renal alpha-2 adrenoceptors in conscious, euvolumic rats modulates the reabsorption of water and sodium at the site of the renal nephron.

Adrenergic alpha-Agonists↗

PubMed1986

Influence of oxytocin on renal hemodynamics and electrolyte and water excretion.

We examined the renal effects of synthetic oxytocin (OT) in the presence and absence of vasopressin in conscious euvolemic rats. Both sexes of the Long-Evans (LE) and Brattleboro homozygous (DI) strains were used. OT infused intravenously at 0.25 and 2.5 ng X min-1 X 100 g body wt (BW)-1 resulted, respectively, in plasma concentrations of 30 +/- 6 and 265 +/- 88 pg/ml in LE rats and 46 +/- 5 and 327 +/- 29 pg/ml in DI rats. Glomerular filtration rate (GFR) was augmented most consistently by the larger dose of hormone in LE rats (P less than 0.05), whereas the low infusion rate of OT enhanced GFR in DI rats (P less than 0.01). Effective renal plasma flow was not changed significantly. OT (both doses) increased the fractional excretion of sodium two- to threefold in each strain of animal (all at least P less than 0.05 from control), whereas the fractional excretion of potassium was largely unaffected. In LE rats, a diuresis was observed with either infusion rate of hormone, accompanied by a rise in osmolar clearance (COsm). In contrast, there was no change of urine flow with the low dose of OT in DI rats, because COsm increased and the clearance of free water (CH2O) decreased proportionately. The higher infusion rate of OT promoted antidiuresis in DI rats, with negative CH2O and little change in COsm. We conclude that oxytocin enhances GFR and is natriuretic regardless of the presence or absence of endogenous vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

The effect of atrial natriuretic factor on blood pressure, heart rate, and renal functions in conscious, spontaneously hypertensive rats.

Atrial natriuretic factors, polypeptides released by atrial myocytes, may play a role in the control of blood pressure and the regulation of renal salt and water excretion. Our studies were designed to assess the role of a synthetic peptide, atriopeptin II, on blood pressure and heart rate, renal hemodynamics, and salt and water excretion in conscious, spontaneously hypertensive rats and in normotensive Wistar-Kyoto rats. Changes in mean arterial pressure and heart rate were recorded following intravenous bolus injections (0.1, 1.0, 10, 100 micrograms/kg) of atriopeptin II in 5 spontaneously hypertensive and 5 Wistar-Kyoto rats. In a second group of rats the peptide was infused for 90 minutes in two different doses: low dose, 1 microgram/kg + 2 micrograms/kg/hr; and high dose, 10 micrograms/kg + 20 micrograms/kg/hr. Bolus injections of atriopeptin II resulted in dose-dependent decreases in mean arterial pressure in the hypertensive, but not in the normotensive, rats; heart rates remained unchanged. Blood pressure decreased gradually during the sustained infusion of both doses of atriopeptin II, with the spontaneously hypertensive strain showing increased sensitivity compared to the Wistar-Kyoto strain. Heart rate decreased in both strains during infusion of the high dose; the decrease was significant only in the hypertensive rats. The low dose of atriopeptin II increased the clearance of free water in both strains of rats; sodium excretion was increased only in the hypertensive rats. The high-dose atriopeptin II was associated with transient natriuresis, unaltered glomerular filtration rate, and decreased effective renal blood flow in both strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Contrasting views on the action of atrial peptides: lessons from studies of conscious animals.

In a rather short time, a consensus seems to have emerged among researchers regarding the mechanisms of the natriuretic and hypotensive actions of atrial natriuretic factor (ANF). According to the by now classic view, the natriuresis induced by ANF is mediated by changes in renal hemodynamics; vasorelaxation is proposed as the primary mechanism of its hypotensive action. Recent evidence, mostly from experiments with conscious animals, does not support this view. Results from experiments performed with chronically instrumented spontaneously hypertensive rats and normotensive (Wistar-Kyoto and Wistar) rats show that the natriuresis induced by a synthetic ANF is not accompanied by increases in glomerular filtration rate or renal blood flow. Measurement of cardiac output (CO) and blood pressure indicate that a decrease in CO, not a fall in total peripheral resistance, is the cause of the decrease in blood pressure. Based on this and other available evidence, a hypothetical scheme for the biological role of ANF is proposed.

Animals↗

PubMed1986

Renal response to pentobarbital anesthesia in rats: effect of interrupting the renin-angiotensin system.

The influence of interrupting the renin-angiotensin system on the renal hemodynamic response to barbiturate anesthesia was assessed in conscious, trained, chronically catheterized rats. Anesthesia induced by pentobarbital caused a marked reduction in mean arterial pressure, heart rate, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Pretreatment of rats with captopril, an inhibitor of angiotensin I converting enzyme, prevented the impairment of renal hemodynamics by pentobarbital without restoring blood pressure. GFR remained at 100 to 110% of control values in captopril-pretreated rats receiving pentobarbital, but was reduced by pentobarbital (90-120 min after induction) to 75 +/- 5% in rats which did not receive captopril. ERPF showed similar changes. An antagonist of angiotensin II receptors, 1-sarcosine-8-isoleucine-angiotensin II, did not prevent the anesthesia-induced decrements in GFR and ERPF (GFR was reduced to 78 +/- 6% and ERPF to 68 +/- 4% at 90-120 min after pentobarbital). This failure of the antagonist of angiotensin II receptors to protect renal hemodynamics may have been due to its intrinsic agonist activity on the renal vasculature. This is suggested by the fact that, in captopril-pretreated rats, which maintained renal hemodynamics in response to pentobarbital, addition of 1-sarcosine-8-isoleucine-angiotensin II caused a reduction in GFR and ERPF and an elevated blood pressure. At 100 min after administration of pentobarbital, plasma renin activity was elevated compared to a conscious control group (3.57 +/- 0.42 vs. 1.94 +/- 0.34 ng angiotensin l/ml X hr, P less than .05). It is concluded that the renin-angiotensin system mediates an impairment of renal hemodynamics during pentobarbital anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Sarcosine-8-Isoleucine Angiotensin II↗

PubMed1984

Influence of vasopressin on renal hemodynamics in conscious Brattleboro rats.

The influence of vasopressin on renal hemodynamics was assessed by treating conscious Brattleboro homozygotes (DI rats) both acutely and chronically with physiologic doses of vasopressin. Intravenous infusions of vasopressin for 1 h, resulting in plasma vasopressin concentrations of less than 1.25, 2.3, and 8.0 pg/ml, respectively, failed to change glomerular filtration rate (GFR) or effective renal blood flow (ERBF) significantly, nor were there significant changes during 5 h of infusion. Body weight was not altered during these infusions. When synthetic vasopressin was given by osmotic minipumps for 10 days, with the rats gaining weight and thus changing the volume of their body fluids, GFR and ERBF increased significantly, by approximately 45 and 55%, respectively. Acute administration of volume alone, as well as acute vasopressin plus acute administration of volume, did not alter GFR or ERBF significantly. The data are compatible with the view that vasopressin, in physiologic plasma concentrations, exerts an influence on renal hemodynamics, that may be mediated through the long-term alteration of body fluid volumes. Alternatively or additionally, prolonged exposure of DI rats to vasopressin may increase their renal hemodynamics through tubuloglomerular feedback.

Animals↗

PubMed1984

Renal autoregulation in chronically catheterized conscious rats.

We examined renal hemodynamics and arterial plasma renin activity (PRA) concurrently in trained chronically catheterized conscious rats during decreased and elevated renal arterial pressure (RAP). Control RAP had an absolute value of 112 +/- 2 mmHg (mean +/- SE). During inflation of a suprarenal aortic cuff, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were autoregulated down to 82% of control RAP. Within this range GFR averaged 107 +/- 5% and ERPF 114 +/- 10% of the control value. During inflation of the infrarenal aortic cuff, RAP increased by 24 +/- 2% to an absolute level of 139 +/- 5 mmHg; this elevation was associated with autoregulation of both GFR (100 +/- 5% of control) and ERPF (94 +/- 6% of control). Arterial PRA had an absolute value during control conditions of 2.1 +/- 0.2 ng ANG I X ml-1 X h-1. It was not significantly altered within the autoregulatory range, being 104 +/- 10% of control during lowered RAP and 120 +/- 15% of control during elevated RAP. Nor, in separate experiments, was PRA changed significantly during the transient state, i.e., at 5, 10, or 30 min after RAP was lowered to an autoregulatory level. These studies demonstrate that, in the conscious rat, there is considerable autoregulatory capacity both below and above resting arterial pressure, and that GFR and ERPF are autoregulated concomitantly. Arterial PRA was not altered significantly within the autoregulatory range.

Animals↗

PubMed1983

Renal hemodynamics in conscious rats: effects of anesthesia, surgery, and recovery.

The influence of barbiturate anesthesia and minor surgical incisions on renal function was assessed in trained, chronically catheterized rats. In addition, renal hemodynamic changes during recovery from ether anesthesia and surgery were examined. Administration of pentobarbital in the chronic animals was associated with a marked reduction in arterial pressure (108 +/- 5 vs. 85 +/- 2 mmHg, P less than 0.01), renal blood flow (8.28 +/- 0.50 vs. 6.20 +/- 0.53 ml X min-1 X 100 g body wt-1, P less than 0.01), and glomerular filtration rate (1.30 +/- 0.10 vs. 0.97 +/- 0.11 ml X min-1 X 100 g body wt-1, P less than 0.01). Responses to Inactin were essentially identical. Small skin incisions during barbiturate anesthesia caused blood pressure to rise, but did not significantly change renal function parameters from already reduced values. In rats studied 2 h after ether anesthesia and surgical placement of catheters, arterial pressure was elevated compared with the same rats studied 4-7 days later (127 +/- 3 vs. 109 +/- 3 mmHg, P less than 0.005). Renal blood flow (5.80 +/- 0.37 vs. 8.90 +/- 0.93 ml X min-1 X 100 g body wt-1, P less than 0.01) and glomerular filtration rate (0.81 +/- 0.07 vs. 1.05 +/- 0.08 ml X min-1 X 100 g body wt-1, P less than 0.001) were markedly depressed during the recovery from surgery. It is concluded that barbiturate anesthesia depresses renal function in rats. This impairment should be considered when interpreting experiments that must be performed under anesthesia. In addition, the "conscious" preparation commonly used for renal studies in rats, i.e., one involving experimentation 2-3 h after ether anesthesia and surgery, is associated with a severe depression of renal hemodynamics.

Anesthesia, General↗