Biomedical subjects

B A Benjamin

Publications and source records attributed to B A Benjamin.

At least 19 recordsLinked to original sources

PubMed1998

Peptide YY inhibits vasopressin-stimulated chloride secretion in inner medullary collecting duct cells.

mIMCD-k2 cells are derived from the inner medullary collecting duct of a mouse and exhibit electrogenic sodium absorption and cAMP- and vasopressin (AVP)-stimulated electrogenic chloride secretion [N. L. Kizer, B. Lewis, and B. A. Stanton. Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F347-F355, 1995; and N. L. Kizer, D. Vandorpe, B. Lewis, B. Bunting, J. Russell, and B. A. Stanton. Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F854-F861, 1995]. The purpose of the present study was to determine how peptide YY (PYY) affects electrogenic Na+ and Cl- current in mIMCD-k2 cells. Short-circuit currents (Isc) were measured across monolayers of mIMCD-k2 cells mounted in Ussing-type chambers. PYY did not alter baseline Isc, nor did it alter Isc in chloride-free conditions, indicating no effect on electrogenic sodium transport. Baseline chloride current in these cells is low; therefore, chloride short-circuit current (IClsc) was stimulated with AVP (10 nM) added to the basolateral surface and 10 microM amiloride added to the apical surface. Although apical applications of PYY had no effect, basolateral application of PYY caused attenuation of IClsc, with the maximal inhibitory dose (100 nM) causing 52 +/- 1.3% inhibition (IC50 = 0.11 nM). Inhibition by PYY of IClsc is mediated through the Y2 receptor subtype, as PYY-(3-36) was the only PYY analog tested that caused inhibition and was equipotent to PYY. Inhibition by PYY of IClsc was abolished following incubation with pertussis toxin. We also show that PYY inhibits AVP-stimulated cAMP accumulation, with a maximal inhibitory dose (100 nM) causing a 38% +/- 6% inhibition (IC50 = 0.16 nM), comparable to inhibition by PYY of IClsc. We conclude that PYY acts through either Gi or Go to inhibit adenylate cyclase activity, leading to a decrease in AVP-stimulated chloride current.

Adenylate Cyclase Toxin↗

PubMed1997

A quantitative description of the Na-K-2Cl cotransporter and its conformity to experimental data.

In epithelia, the Na-K-2Cl cotransporter cooperates with other transport mechanisms to produce transepithelial NaCl transport. The reaction cycle for the Na-K-2Cl cotransporter has been established experimentally, but whether it accounts, quantitatively, for experimental findings has yet to be established. The differential equations that describe the reaction cycle were formulated, and the steady-state solutions were obtained by digital computation. Conformity between this description and the experimental data obtained from the literature was explored by automatic searches for the sets of rate constants that yielded statistical best-fits to the experimental data. Fits were obtained from renal epithelial cell lines, HeLa cells, and duck erythrocytes. Results show that the reaction cycle for the Na-K-2Cl cotransporter conforms well, quantitatively, with the experimental data.

Animals↗

PubMed1997

Peptide YY receptor distribution and subtype in the kidney: effect on renal hemodynamics and function in rats.

This study characterizes the location and subtype of peptide YY (PYY) receptors in rat and rabbit kidney and the effect of PYY on renal function and renal hemodynamics in rats. Receptor autoradiography performed on kidney sections revealed a dense concentration of specific high-affinity binding sites [dissociation constant (Kd) = 0.7 +/- 0.1 nM] in the papilla of the rat, as well as cortical and papillary binding in the rabbit (papilla, Kd = 1.6 +/- 0.6 nM) and some medullary binding in both species. In the rat papilla, neuropeptide Y (NPY) and the Y1 agonist [Leu31,Pro34]NPY competed with PYY for binding (Kd = 1.1 +/- 0.4 nM and 1.6 +/- 0.5 nM, respectively), but NPY-(13-36) (Y2 agonist) and pancreatic polypeptide (PP, Y4 agonist) were without effect, demonstrating that the PYY receptor in the rat papilla is of the Y1 subtype. In the rabbit papilla, NPY and NPY-(13-36) competed with PYY (Kd = 0.5 +/- 0.1 and 3.1 +/- 0.6 nM, respectively), but [Leu31,Pro34]NPY and PP were without effect, evidence that the PYY receptor in the rabbit papilla is of the Y2 subtype. Infusion of PYY into rats (47 pmol x kg(-1) x min[-1]) increased mean arterial pressure (103 +/- 6 to 123 +/- 8 mmHg) and decreased renal plasma flow (13 +/- 1.8 to 8.4 +/- 2.1 ml/min) but produced no significant change in glomerular filtration rate or sodium excretion. Injection of PYY or angiotensin II directly into the renal artery caused a dose-related vasoconstriction, which was less intense but of longer duration for PYY than for angiotensin II. These results show that receptors for PYY are widely distributed in the kidney and that exogenously administered PYY causes renal vasoconstriction and may influence renal sodium excretion.

Animals↗

PubMed1995

Effects of ANF prohormone peptides in conscious primates.

1. Recent studies suggest that amino-terminal peptides from the atrial natriuretic factor (ANF) prohormone are natriuretic. 2. The effects of pro ANF 31-67 and ANF 99-126 on renal function were studied in conscious non-human primates (Macaca fascicularis). 3. Results show that pro ANF 31-67 and ANF 99-126 are diuretic and natriuretic and that when the two peptides are given in combination sodium excretion increases in an additive fashion. 4. These results indicate that multiple peptides from the ANF prohormone are natriuretic. Furthermore, these findings suggest that the combined action of these peptides causes the natriuresis that occurs after the release of endogenous atrial peptides.

Animals↗

PubMed1995

Effect of proANF-(31--67) on sodium excretion in conscious monkeys.

The purpose of this study was to determine the effect of proANF-(31--67) on renal function in conscious, chronically instrumented monkeys (Macaca fascicularis). The experimental protocol consisted of a 30-min control period followed by 60 min of peptide infusion and a 30-min recovery period. Atrial natriuretic factor (ANF)-(99--126), proANF-(31--67), of a combination of ANF-(99--126) plus proANF-(31--67) was infused at 15 pmol.kg-1.min-1. ANF-(99--126) caused sodium excretion to increase from 12.5 +/- 3 to a peak of 37.9 +/- 10.4 mueq/min, whereas fractional sodium excretion (FENa) increased from 0.69 +/- 0.2 to 2.3 +/- 0.43%. ProANF-(31--67) increased sodium excretion from 12.7 +/- 5 to a peak of 23.3 +/- 9.0 mueq/min and FENa from 0.56 +/- 0.07 to a peak of 1.15 +/- 0.4%. When ANF-(99--126) and proANF-(31--67) were infused in combination, sodium excretion increased from 9.6 +/- 3 to a peak of 5.19 +/- 12.5 mueq/min, whereas FENa increased from 0.97 +/- 0.4 to 3.9 +/- 1.1%. Mean arterial pressure decreased by approximately 10 mmHg in all three groups. These findings indicate that intravenously administered proANF-(31--67) causes an increase in sodium excretion and that when proANF-(31--67) and ANF-(99--126) are given in combination, they act in an additive fashion to increase renal sodium excretion.

Animals↗

PubMed1994

Effect of bilateral atrial appendectomy on postprandial sodium excretion in conscious monkeys.

We have shown that bilateral atrial appendectomy attenuates the increase in atrial natriuretic factor and sodium excretion that occurs after acute blood volume expansion. These findings suggest that the atrial appendages influence renal sodium excretion. The purpose of the present study was to determine whether atrial appendectomy alters the increase in sodium excretion that occurs postprandially. One to two weeks after surgery, conscious monkeys (Macaca fascicularis) were given a meal through a nasogastric tube. The meal consisted of water (20 ml/kg), sodium (2.5 mmol/kg), carbohydrate (2.65 g/kg), protein (0.68 g/kg), and fat (0.89 g/kg). Postprandial changes in renal function were monitored for 210 min after the meal was started. In the sham animals, urine flow increased from 0.23 +/- 0.04 to 0.55 +/- 0.05 ml/min, sodium excretion increased from 28.6 +/- 7.8 to 84.4 +/- 12.3 mumol/min and fractional sodium excretion increased from 1.35 +/- 0.38% to 3.06 +/- 0.43%. Bilateral atrial appendectomy (ATX) significantly attenuated the renal responses to the meal. Urine flow in the ATX animals increased from 0.19 +/- 0.03 to 0.30 +/- 0.02 ml/min, sodium excretion increased from 26.5 +/- 5.8 to 45.8 +/- 15.2 mumol/min, and fractional sodium excretion increased from 0.99 +/- 0.02% to 1.53 +/- 0.34%. Postprandial changes in renal and systemic hemodynamics were also monitored and were similar in both groups. Plasma levels of atrial natriuretic factor were also similar in both groups and did not increase postprandially. These findings demonstrate that bilateral atrial appendectomy attenuates postprandial-induced increases in sodium excretion by mechanisms that do not involve an increase in atrial natriuretic factor.

Animals↗

PubMed1992

The heart and control of renal excretion: neural and endocrine mechanisms.

There has been a great deal of research concerning the heart being an important regulator of renal fluid and electrolyte excretion. This cardiac-renal connection involves two different types of major mechanisms, both of which are covered in this review. The first of these to be discovered was neural reflex regulation. This type of control is due to the fact that the heart possesses nerve receptors whose activity is altered by changes in the degree of cardiac stretch that occur as a result of changes in blood volume. These receptors affect various humoral, neural, and perhaps hemodynamic mechanisms that modify renal excretion. A second, more recently discovered type of regulation is based on the concept that the heart is also an endocrine gland. Similar to neural receptor activity, cardiac hormone secretion is also linked to the degree of cardiac stretch or filling. These cardiac peptides have been shown to have a variety of physiologic effects, most of which directly or indirectly affect renal excretion. Both of the above cardiorenal control mechanisms, one neural and one humoral, may be important not only in maintaining normal fluid-electrolyte balance but may also have pathophysiologic relevance.

Animals↗

PubMed1991

Renal nerves and postprandial renal excretion in the conscious monkey.

Experiments were performed in conscious macaque monkeys to determine if the renal nerves are important in mediating postprandial increases in renal fluid-electrolyte excretion in this species. Monkeys were given a high-sodium meal via a nasogastric tube. Consecutive 10-min urine samples were taken during the 30-min time of meal administration and then 180 min postprandially. The experiment was performed both before and 10-14 days after each animal underwent renal denervation. Diuresis and natriuresis occurred under both renal-innervated and -denervated conditions. However, the amounts of urine and sodium excreted were less after renal denervation. For the total 210 min of measurements obtained after the meal was started, cumulative urine output was 95.0 +/- 26.4 ml and sodium excretion 7.18 +/- 1.74 meq in innervated kidneys vs. 56.7 +/- 7.0 ml (a 40% decrease; P less than 0.005) and 4.84 +/- 0.99 meq (a 33% decrease; P less than 0.01) after denervation. These results demonstrate that the renal nerves are important in the nonhuman primate for eliciting the postprandial changes in urinary excretion secondary to intake of a high-sodium meal.

Animals↗

PubMed1990

Haemodynamic and ADH responses to central blood volume shifts in cardiac-denervated humans.

Haemodynamic responses and antidiuretic hormone (ADH) were measured during body position changes designed to induce blood volume shifts in 10 cardiac transplant recipients to assess the contribution of cardiac and vascular volume receptors in the control of ADH secretion. Each subject underwent 15 min of a control period in the seated posture, then assumed a lying posture for 30 min at 6 degrees head-down tilt (HDT) followed by 30 min of seated recovery. Venous blood samples and cardiac dimensions (echocardiography) were taken at 0 and 15 min before HDT, 5, 15 and 30 min of HDT, and 5, 15 and 30 min of seated recovery. Blood samples were analysed for haematocrit, plasma osmolality, plasma renin activity (PRA) and ADH. Resting plasma volume (PV) was measured by Evans blue dye and per cent changes in PV during posture changes were calculated from changes in haematocrit. Heart rate (HR) and blood pressure (BP) were recorded every 2 min. In the cardiac transplant subjects, mean HR decreased (BP less than 0.05) from 102 b.p.m. pre-HDT to 94 b.p.m. during HDT and returned to 101 b.p.m. in seated recovery while BP was slightly elevated (P less than 0.05). PV was increased by 6.3% (P less than 0.05) by the end of 30 min of HDT but returned to pre-HDT levels following seated recovery. Plasma osmolality was not altered by posture changes. Mean left ventricular end-diastolic volume increased (P less than 0.05) from 90 +/- 5 ml pre-HDT to 105 +/- 4 ml during HDT and returned to 88 +/- 5 ml in seated recovery. Plasma ADH was reduced by 28% (P less than 0.05) by the end of HDT and returned to pre-HDT levels with seated recovery. PRA was also reduced by 28% (P less than 0.05) with HDT. These responses were similar to those of six normal cardiac-innervated control subjects and one heart-lung recipient. Therefore, cardiac volume receptors are not the only mechanism for the control of ADH release during acute blood volume shifts in man.

Adult↗

PubMed1990

Atriopeptin does not augment the transvascular flux of macromolecules in the hamster cheek pouch.

Natriuretic peptides elaborated by atrial myocytes promote marked renal sodium and water excretion as a mechanism for fluid and electrolyte balance. Recent evidence suggests that atriopeptin (ANP) also targets the non-renal vasculature as a site for enhanced fluid exchange. It remains unclear whether ANP alters microvascular integrity to facilitate the efflux of both plasma and proteins across the endothelial barrier, or if fluid exchange is selectively enhanced. This study evaluated the influence of ANP on macromolecular transport through the direct observation of microvessels in the hamster cheek pouch using fluorescent intravital microscopy. Fluorescein isothiocyanate conjugated to either bovine serum albumin or dextran 150,000 Mw was utilized as a permeability probe. Macromolecular efflux was quantified as fluorochrome clearance. The clearance of fluorescein-conjugated bovine serum albumin (57.94 +/- 7.03) or fluorescein-conjugated dextran 150 (4.09 +/- 1.35) remained unaltered by intravascular injection of 1 microgram/kg ANP. Topical application of 40 ng to cheek pouch microvessels produced similar results. All pouches demonstrated positive leakage response to histamine 2.5 x 10(-6) M, increasing fluorochrome clearance approximately 2- to 11-fold. Bolus injection of 1 microgram/kg ANP reduced mean arterial pressure, increased urine flow from 6.63 +/- 2.59 microliters/min to 8.20 +/- 6.13 microliters/min, and elevated sodium excretion from 1.37 +/- 0.49 microEq/min to 2.54 +/- 0.99 microEq/min. These results suggest that ANP fails to significantly alter the integrity of the protein-transporting channels in the microvascular exchange barrier.

Animals↗

PubMed1988

Chronic atrial appendectomy alters sodium excretion in conscious monkeys.

The purpose of this study is to determine whether chronic removal of atrial appendages alters renal response to volume expansion in the conscious monkey. Chronic bilateral atrial appendectomy (ATX) was performed in six animals. Six additional animals served as sham-operated controls. Monkeys were studied 1-2 wk after chronic surgery. The protocol consisted of three consecutive 10-min urine collections followed by 20% ischemic blood volume expansion (VE) and 120 min of post-VE measurements. In sham animals, VE caused an increase in plasma atrial natriuretic peptide (ANP) levels (48 +/- 7 pg/ml to a peak of 108 +/- 34 pg/ml). Urine flow increased from 0.43 +/- 0.07 to 1.07 +/- 0.24 ml/min, sodium excretion increased from 17.9 +/- 2.6 to 74.9 +/- 12.0 mu eq/min, and fractional sodium excretion increased from 0.67 +/- 0.10 to 2.43 +/- 0.28%. ATX attenuated the increase in ANP (34 +/- 8 pg/ml to a peak of 38 +/- 9 pg/ml) in four of six animals. In these animals, renal response to VE was significantly attenuated. Urine flow increased from 0.21 +/- 0.05 to 0.30 +/- 0.01 ml/min, sodium excretion increased from 19.3 +/- 6.02 to 37.8 +/- 5.05 mu eq/min, and fractional sodium excretion increased from 0.79 +/- 0.08 to 1.43 +/- 0.17%. Renal response of two ATX animals with normal increases in atrial natriuretic factor was similar to the sham group. Effect of volume expansion on mean arterial pressure, central venous pressure, and renal hemodynamics was not altered by ATX. These findings demonstrate that bilateral atrial appendectomy in the monkey attenuates the increase in ANP and reduces renal response to VE.

Animals↗

PubMed1988

Renal nerves and renal responses to volume expansion in conscious monkeys.

Experiments were performed in conscious macaque monkeys to determine the effect of renal denervation on the diuresis and natriuresis of blood volume expansion. When the kidneys were innervated, expansion of estimated blood volume by 20% with 3% dextran in isotonic saline caused increases in urine flow (V), from 0.28 +/- 0.07 ml/min to a peak response of 1.08 +/- 0.20 ml/min, absolute sodium excretion (UNaV), from 30.0 +/- 11.2 to 99.8 +/- 11.7 mueq/min, and fractional sodium excretion (FENa+), from 1.24 +/- 0.51 to 3.19 +/- 0.56%. The animals then underwent bilateral renal denervation and were volume expanded a second time 6-13 days postdenervation. Under this condition, V increased from 0.32 +/- 0.05 to 0.64 +/- 0.08 ml/min, UNaV, from 22.2 +/- 4.6 to 46.2 +/- 8.0 mueq/min, and FENa+, from 0.91 +/- 0.26 to 1.92 +/- 0.41%, these increases being significantly less than when the kidneys were innervated. These results demonstrate that the renal nerves play an important role in the nonhuman primate in mediating increases in renal excretion during hypervolemia.

Animals↗

PubMed1987

Renal response to volume expansion in atrial-appendectomized dogs.

The purpose of this study was to determine whether chronic removal of the atrial appendages alters the renal response to volume expansion (VE) in anesthetized dogs. Chronic bilateral atrial appendectomy (ATX) was performed in 10 animals. Six animals served as sham-operated controls (S). The animals were studied 10-14 days after chronic surgery. The protocol consisted of a 20-min control period followed by isochemic VE (20%) and 120 min of post-VE measurements. The dogs were studied a second time, 2 wk later, after acute bilateral cervical vagotomy. Results from the vagi-intact study showed that VE caused a diuresis, natriuresis, and increase in fractional sodium excretion in ATX that did not differ from the response observed in S. VE also caused equivalent increases in central venous and mean arterial pressures in S and ATX. Atrial appendectomy, however, failed to significantly attenuate the increase in atrial natriuretic factor (ANF) after VE. Plasma ANF increased from 27.2 +/- 4.8 to 47.0 +/- 7.3 pg/ml in ATX and from 27.2 +/- 7.8 to 59.0 +/- 17.9 pg/ml in S. After vagotomy, VE caused transient increases in urine flow and sodium excretion. The changes in central venous and mean arterial pressures were not different from the vagi-intact study and vagotomy did not affect the increase in ANF after VE. Circulating ANF levels increased from 26.4 +/- 5.5 to 75.0 +/- 14.0 pg/ml in ATX and from 28.1 +/- 5.7 to 73.0 +/- 22.6 pg/ml in S. These results demonstrate that, in the dog, bilateral ATX does not alter the renal response to volume expansion or attenuate the increase in ANF. In addition, these results show that vagal pathways are not required for the release of ANF and that vagotomy fails to uncover any effect of atrial appendectomy on renal function.

Animals↗

PubMed1987

Effect of vagotomy and thoracic sympathectomy on responses of the monkey to water immersion.

Cardiopulmonary stretch receptors have been implicated as part of a reflex mechanism linking changes in blood volume to changes in renal excretion. Experiments were performed to determine whether total denervation of these receptors by combined cervical vagotomy and thoracic sympathectomy affects the renal responses of the monkey to head-out water immersion, a maneuver that translocates blood to the thorax and elicits an increase in renal salt and water excretion. Macaca fascicularis monkeys first underwent chronic bilateral thoracic sympathectomy or sham denervation performed in two stages a week apart. One to two weeks later, they were anesthetized with pentobarbital sodium, and the sympathectomized animals underwent bilateral cervical vagotomy. Control renal function did not differ between the two groups. Immersion of 90-min duration increased central venous and mean arterial pressures by similar amounts in both groups, but heart rate increased only in the sham-denervated animals. Denervation did not affect the magnitudes or delay the times of onset of the increases in urine flow, absolute and fractional sodium excretion, and osmolar and free water clearances occurring with immersion. These results demonstrate that in the anesthetized monkey cardiopulmonary receptors are not necessary for eliciting the renal responses to immersion.

Animals↗

PubMed1987

Cardiovascular results from a rhesus monkey flown aboard the Cosmos 1514 spaceflight.

Pressure and flow relationships to the head were measured before and during spaceflight by means of a chronically implanted cuff placed about the left common carotid artery in one of two rhesus monkeys flown aboard Cosmos 1514. Measurements were obtained daily for 4 min every 2 h during the 5-d spaceflight and compared to identical recordings obtained during a 35-h pre-flight control period 9 d before flight and a 12-h period while on the launch pad. Mean arterial pressure demonstrated a 10% increase compared to control levels immediately on insertion into orbit and maintained a 16-27% increase over the first few hours of flight before returning to baseline levels. Blood flow velocity showed a marked increase (approximately 8 cm/s) compared to pre-flight control while on the launch pad which was maintained over the duration of the flight. Blood flow showed reciprocal changes to pressure on orbital insertion. Cardiovascular system changes persisted into the second day of flight and were most clearly indicated by a decrease in relative differences between blood flow to the head and total cardiac output as measured by impedance plethysmography. Signs of adaptation appeared on days 3-5 of flight.

Animals↗

PubMed1984

Role of cardiac volume receptors in the control of ADH release during acute simulated weightlessness in man.

Hemodynamic responses and antidiuretic hormone (ADH) were measured during body position changes designed to induce central blood volume shifts in ten cardiac and one heart-lung transplant recipients to assess the contribution of cardiac volume receptors in the control of ADH release during the initial acute phase of exposure to weightlessness. Each subject underwent 15 min of a sitting-control period (C) followed by 30 min of -6 degrees headdown tilt (T) and 30 min of resumed sitting (S). Venous blood samples and cardiac dimensions were taken at 0 and 15 min of C; 5, 15, and 30 min of T; and, 5, 15, and 30 min of S. Blood samples were analyzed for hematocrit, plasma osmolality, plasma renin activity (PRA), and ADH. Heart rate (HR) and blood pressure (BP) were recorded every two min. Plasma osmolality was not altered by posture changes. Mean left ventricular end-diastolic volume increased (P < .05) from 90 ml in C to 106 ml in T and returned to 87 ml in S. Plasma ADH was reduced by 20% (P < .05) with T and returned to control levels with S. These responses were similar in six normal cardiac-innervated control subjects. These data may suggest that cardiac volume receptors are not the primary mechanism for the control of ADH release during acute central volume shifts in man.

Adult↗

PubMed1982

Does LD100 E coli shock cause myocardial failure?

We have documented that myocardial dysfunction occurs in canine endotoxin shock and have designed this study to determine the effect of lethal live E coli-induced shock on the myocardium. Small adult heart "donor" dogs (wt range 6-9 kg) were infused with LD100 E coli (N = 12) or saline (N = 16) for 30 minutes. Two hours later, heart transfer surgery was initiated and once completed the isolated working left ventricle was allowed to equilibrate in the extracorporeal circuit of a "support" dog (wt range 22-32 kg). Myocardial performance was then evaluated by changing mean aortic pressure while controlling cardiac output. Three to five hours after E coli infusion, marked myocardial dysfunction occurred in 75% of the hearts as evidenced by increased left ventricular and diastolic pressures and depressed peak positive and negative dP/dt at every mean aortic pressure tested compared with control hearts. Myocardial efficiency and power were depressed, oxygen uptake was elevated, and coronary blood flow was unchanged in E coli-treated compared with control hearts. Data support the presence of heart dysfunction in gram-negative septic shock.

Animals↗

PubMed1981

Vasopressin release during sepsis and septic shock in baboons and dogs.

Plasma vasopressin concentration was measured by radioimmunoassay in lightly anesthetized baboons and dogs before and during experimental Escherichia coli septic shock. Since vasopressin is a potent vasoconstrictor, and activator of clotting factors and a myocardial depressant, we postulated that, if found in substantial amounts in the plasma, vasopressin may contribute to the physiopathology of the septic shock syndrome. Quite high plasma vasopressin concentrations were found in both baboons and dogs. In the baboons, increased plasma vasopressin concentrations occurred, while mean arterial blood pressure was still within normal limits and remained elevated for as long as 12 hours during septic shock. Plasma vasopressin concentrations of this magnitude have been previously reported only with direct hypothalamic stimulation or after hypotensive shock secondary to hemorrhage.

Animals↗