Biomedical subjects

A J Premen

Publications and source records attributed to A J Premen.

27 records · Page 2Linked to original sources

PubMed1985

Maintenance of renal autoregulation during infusion of aminophylline or adenosine.

Adenosine has been postulated to link control of glomerular filtration rate (GFR) and renal blood flow (RBF) with changes in renal metabolism. In the present study, we examined the role of adenosine in renal autoregulation by comparing the responses of normal anesthetized dogs to step decreases in renal artery pressure (RAP) to the response obtained after receptor blockade of adenosine with aminophylline or by flooding the kidney with exogenous adenosine. In six dogs at normal RAP, intrarenal infusion of aminophylline (10 mumol/min) did not alter renal hemodynamics. GFR and RBF were well autoregulated (greater than 90% of control) at RAP values equal to or greater than 85 mmHg before and after aminophylline. At RAP equal to 75 mmHg, GFR and RBF decreased by 27 +/- 10 and 20 +/- 8%, respectively, before aminophylline and by 25 +/- 7 and 13 +/- 6% after aminophylline. In a different group of six dogs, intrarenal infusion of adenosine (6 mumol/min) significantly increased RBF (32 +/- 9%) and decreased GFR (38 +/- 10%) at normal RAP. However, GFR and RBF were both well autoregulated (greater than 90% of control) at RAP values equal to or greater than 85 mmHg before and after adenosine. At RAP equal to 75 mmHg, GFR and RBF decreased by 10 +/- 5 and 7 +/- 3%, respectively, before adenosine and by 12 +/- 6 and 17 +/- 5% after adenosine. Neither aminophylline nor adenosine attenuated the elevations in plasma renin activity associated with reductions in RAP. These data fail to provide evidence that adenosine is an important factor in autoregulation of GFR and RBF during acute reductions in RAP within the autoregulatory range.

Adenosine↗

PubMed1985

Postprandial regulation of renal hemodynamics: role of pancreatic glucagon.

The aim of this study was to ascertain the quantitative importance of glucagon in mediating protein-induced increases in renal blood flow (RBF) and glomerular filtration rate (GFR) during the postprandial state. Six chronically instrumented conscious dogs were each subjected to four protocols: normal protein control meal (C); high protein meat meal (M); somatostatin infusion and meat (S + M); and glucagon infusion. C produced small increases in RBF (12 +/- 2%) and GFR (14 +/- 2%) without changing arterial plasma glucagon. M produced marked increases in RBF (38 +/- 4%), GFR (41 +/- 5%), and glucagon (from 23.3 +/- 3.6 to 73.3 +/- 7.1 pg/ml) over a 3-h period. During S + M, RBF and GFR failed to increase while glucagon was suppressed by 36 +/- 8% over a 2-h period. When S was stopped, glucagon rose to 100 +/- 13.9 pg/ml over the next hour, yet RBF and GFR increased by only 14 +/- 4 and 10 +/- 3%, respectively. Glucagon infusion (3 ng X kg-1 X min-1, i.v.) markedly elevated plasma glucagon to 131.6 +/- 27.3 pg/ml, yet neither RBF nor GFR significantly changed. These data indicate that while a protein-rich meat meal does elevate arterial plasma glucagon, the rise is not great enough to elicit significant changes in renal hemodynamics. Thus, elevated plasma levels of glucagon cannot account for protein-mediated increases in RBF and GFR during the postprandial state.

Animals↗

PubMed1985

Importance of the liver during glucagon-mediated increases in canine renal hemodynamics.

We ascertained the importance of the liver in mediating glucagon-induced increases in renal blood flow (RBF) and glomerular filtration rate (GFR) by comparing the renal hemodynamic responses to intrarenal versus intraportal infusion of glucagon at 3 ng X kg-1 X min-1 (a dose previously considered "physiologic") in two separate sets of anesthetized dogs. Following intrarenal infusion for 60 min (n = 6), glucagon was without effect on RBF and GFR. On the average, RBF and GFR increased by only 2 +/- 1 and 3 +/- 1%, respectively. However, in a second group of dogs (n = 6), intraportal infusion of glucagon significantly increased both RBF and GFR by the same order of magnitude over 60 min. RBF and GFR increased, on the average, by 22 +/- 2 and 20 +/- 2%, respectively. Peak responses occurred 30 min following glucagon infusion when RBF and GFR were elevated by 25 +/- 2 and 26 +/- 2%, respectively. In neither group of dogs were filtration fraction, arterial pressure, heart rate, arterial hematocrit, or arterial plasma protein concentration altered. These data indicate that the liver plays an important role in mediating the renal hyperemia and hyperfiltration observed following a physiologic infusion of glucagon.

Animals↗

PubMed1984

Relationship between substance P, intestinal wall compliance and vascular resistance in the canine ileum.

Substance P (SP) is one of many vasoactive peptides found within the gastrointestinal tract with actions on intestinal smooth muscle. Thus, its vasodilatory action could be attenuated through its stimulatory effect on intestinal smooth muscle producing subsequent elevations in extravascular pressure and thus, passively opposing the vasodilation. The aim of this study was to examine for such a possibility for SP by simultaneously assessing ileal perfusion pressure and intestinal wall compliance in the canine ileum during intra-arterial infusion of SP. Infusion of SP at either 0.74 or 7.4 pmol/min significantly decreased ileal perfusion pressure by 8 and 30%, respectively, without affecting wall compliance. During SP infusion at 74 pmol/min, perfusion pressure fell by 49% while wall compliance decreased by 43%, reflecting a significant increase in ileal wall tension. During SP infusion at 7.4 and 74 pmol/min, a 'two-phase' reduction in perfusion pressure was observed. These data suggest that although SP markedly increases ileal wall tension, the elevation in extravascular pressure produced is not strong enough to overcome its potent vasodilatory action in the canine ileum. The potential of a physiologic role for blood-borne SP is discussed.

Animals↗

PubMed1984

Effects of gastrointestinal hormones on ileal vascular and visceral smooth muscle.

Blood levels of gastrin, secretin, gastric inhibitory polypeptide (GIP), and cholecystokinin octapeptide (CCK-8) increase after a meal and may affect vascular and/or visceral smooth muscle. To study this possibility, we measured the effects of local intra-arterial infusion of these hormones on ileal perfusion pressure and intestinal wall compliance. In pentobarbital sodium-anesthetized dogs, a segment of ileum was exteriorized and vascularly perfused at constant flow with arterial blood. Wall compliance was calculated from the pressure generated by incremental changes in intraluminal volume (delta V/delta P). Postprandial blood levels of these hormones did not affect ileal perfusion pressure. However, higher blood levels of secretin and GIP did significantly lower perfusion pressure. Wall compliance was significantly increased by postprandial blood levels of secretin and GIP, while postprandial blood levels of CCK-8 decreased compliance. Gastrin was without effect on compliance. These data suggest these hormones do not contribute to postprandial ileal hyperemia. However, secretin, GIP, and CCK-8 do affect the postprandial activity of ileal visceral smooth muscle.

Animals↗

PubMed1984

Histamine-induced fluid efflux in the canine forelimb as affected by carotid occlusion or hemorrhage.

Infusion of catecholamines concurrently with histamine into the forelimb of the dog prevents histamine-induced increases in lymph flow, protein concentration and forelimb weight. This study tested whether the sympathoadrenal discharge of catecholamines induced by carotid occlusion or hemorrhage would similarly prevent histamine's actions in the canine forelimb. Carotid occlusion or hemorrhage, begun after 30 minutes of histamine infusion (4 micrograms base/min), resulted in a reduction in lymph flow but lymph protein concentration was not changed. Infusion of histamine into the forelimb for 30 minutes in control studies caused the forelimb to gain weight. In experimental studies hemorrhage, begun at one minute after the start of histamine significantly reduced this weight gain but occlusion of the carotid arteries at one minute after the start of histamine did not significantly affect weight gain. These results show that sympathetic nerve activity can lower elevated lymph flow and that sympathetic activity due to hemorrhage reduces the accumulation of interstitial fluid caused by histamine. It seems probable that endogenous catecholamines act directly on filtering vessels to lessen histamine-induced increases in permeability. However, a constriction of lymphatic vessels could have contributed to the reduction in lymph flow and we have no evidence against this possibility.

Animals↗

PubMed1984

Effects of histamine-receptor agonists on transvascular fluid and macromolecular efflux in the canine forelimb.

Histamine increases transvascular fluid and protein efflux in the canine forelimb resulting in edema formation. To clarify the receptor mechanisms of histamine edema, we infused H1 and H2-receptor agonists into the forelimb perfused at constant flow while measuring skin lymph parameters or forelimb weight. The H1-receptor agonist 2(2-pyridyl) ethylamine [PEA] or the H2-receptor agonist 4-methyl histamine (8-40 micrograms/min) singly or in combination fails to increase lymph flow, protein concentration or protein transport. PEA in a dose of 80-400 micrograms/min increases lymph flow, protein concentration and protein transport. 4-Methyl histamine in a dose of 40-200 micrograms/min produces a small but significant decrease in lymph flow and protein transport subsequent to a fall in systemic pressure. 4-Methyl histamine at 40 and 80 micrograms/min produces a progressive and sustained increase in forelimb weight PEA at 40 micrograms/min produces a small increase in forelimb weight which quickly plateaus much like the response seen with acetylcholine (10 micrograms base/min). However, infusion of PEA at 80 micrograms/min progressively increases forelimb weight, similar to that seen with 4-methyl histamine or histamine (1.4 microgram base/min). These data indicate that either H1 or H2-receptor agonists can cause edema formation in the canine forelimb, and imply that histamine edema involves both H1 and H2-receptor interaction.

Animals↗

PubMed1984

Forelimb vascular pressures, skin lymph flow and lymph protein concentration as affected by vasoactive intestinal polypeptide and bombesin.

Vasoactive intestinal polypeptide (VIP) and bombesin are peptides that have been identified in several mammalian tissues including skin. In this study, we have examined the actions of these peptides on forelimb vascular pressures, skin lymph flow, lymph total protein concentration and lymph total protein transport in the canine forelimb perfused at constant arterial inflow. Local intraarterial infusion of sequentially increasing infusion rates of VIP of 300, 600, and 1500 ng/min for twenty minutes at each infusion rate resulted in dose-dependent decreases in forelimb arterial pressures but no change in skin small vein pressure. At the two higher infusion rates, systemic pressure was significantly decreased whereas heart rate significantly increased. Skin lymph parameters were not a significantly altered with the exception of a small but significant decrease in lymph flow at the highest infusion rate of VIP. Infusion of bombesin at 500 ng/min for sixty minutes resulted in significant increases in forelimb arterial and systemic pressures, no change in skin small vein pressure and a significant bradycardia. Skin lymph flow, protein concentration and protein transport were not significantly changed during the infusion of bombesin. These data indicate that while VIP and bombesin possess potent vasodilator and vasoconstrictor effects respectively, they do not significantly affect transmicrovascular fluid and macromolecular efflux in the canine forelimb perfused at constant flow, as assessed by changes in lymph flow and protein concentration.

Animals↗

PubMedDate not supplied

Role of renal hemodynamics and arterial pressure in aldosterone "escape".

This study examined the importance of changes in renal hemodynamics and renal artery pressure (RAP) in allowing the kidneys to escape from the chronic sodium-retaining effects of aldosterone (Aldo). In five dogs in which RAP was permitted to increase during Aldo infusion (14 micrograms/kg/day), sodium excretion (UNaV) and fractional sodium excretion (FENa) decreased markedly on Day 1 and then returned to control on Days 2 to 4 of Aldo infusion as RAP and glomerular filtration rate (GFR) increased 15 to 19 mm Hg and 20% to 24%, respectively, and remained near these levels during 7 days of Aldo infusion. In seven dogs in which RAP was prevented from increasing with an electronically servo-controlled aortic occluder, UNaV decreased from 256 +/- 3 to 117 +/- 9 mEq/day on the first day and remained at 70 to 80 mEq/day below sodium intake for 7 days of Aldo infusion. Cumulative sodium balance and sodium iothalamate space increased 610 +/- 39 mEq and 3729 +/- 397 ml when RAP was servo-controlled, causing ascites in most of the dogs, while mean arterial pressure did not plateau but continued to rise to 59 +/- 3 mm Hg above control after 7 days of Aldo infusion. When the servo-controller was stopped and RAP was allowed to rise while Aldo infusion was continued, GFR rose to 126% to 136% of control, FENa increased markedly, UNaV increased to 579 +/- 64 mEq/day on the first day, and the dogs returned to normal sodium balance. These data indicate that an increase in RAP, which raises GFR and FENa, is essential in allowing the kidneys to escape from the chronic sodium-retaining action of Aldo and to achieve sodium balance and a stable level of arterial pressure without severe volume expansion and ascites.

Aldosterone↗