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A J Premen

Publications and source records attributed to A J Premen.

At least 19 recordsLinked to original sources
PubMed1998

Receptor mechanisms of bradykinin-mediated activation of prenodal lymphatic smooth muscle.

We have previously shown that several endogenous vasoactive agents constrict prenodal lymph vessels in the canine forelimb. In this study, we assessed the receptor mechanisms by which bradykinin activates lymphatic smooth muscle. Intralymphatic (i.l.) infusion of bradykinin at concentrations of 3.82 x 10(-6), 3.82 x 10(-5) and 3.82 x 10(-4) molar significantly increased lymphatic perfusion pressure. To determine the potential role of lymphatic alpha-receptors in this response, we infused bradykinin at a concentration of 3.82 x 10(-4) molar i.l. before and during intra-arterial (i.a.) phentolamine administration. Prior to phentolamine, bradykinin resulted in a doubling of the lymphatic perfusion pressure. Phentolamine alone had no effect on the resting lymphatic pressure, but significantly reduced forelimb arterial pressures. When the infusion of bradykinin was repeated during phentolamine administration, there was no significant change in the lymphatic perfusion pressure. To determine the subclass of alpha-adrenergic receptors involved in this response, we infused bradykinin and the alpha1-receptor agonist phenylephrine i.l. before and during administration of i.a. prazosin, a specific alpha1-receptor antagonist, i.a. Prior to prazosin, both phenylephrine and bradykinin significantly increased lymphatic perfusion pressure. During prazosin administration, neither phenylephrine nor bradykinin significantly altered the lymphatic perfusion pressure. These data indicate that bradykinin-mediated increases in prenodal lymphatic smooth muscle tone are mediated by lymphatic alpha1-adrenergic receptors.

Adrenergic alpha-Agonists↗
PubMed1991

Pancreatectomy, amino acids and glucagon: effect on canine renal autoregulation.

Using pancreactectomized (PX) dogs, we recently suggested the importance of glucagon in modulating amino acid-induced increases in renal blood flow (RBF) and glomerular filtration rate (GFR). We have now ascertained whether glucagon's modulatory effect is associated with an impairment in renal autoregulation. As renal arterial pressure (RAP) was reduced to 70 mmHg (the lower limit of the autoregulatory range) in both sham-operated control (C) and PX control dogs, RBF and GFR remained at values that were greater than 90% of their respective controls. In control dogs infused with amino acids (0.051 mmol/kg per min, i.v.), RBF and GFR rose by 26 and 27%, respectively, at baseline RAP. As RAP was reduced to 70 mmHg, RBF and GFR fell by 25 and 37%, respectively. In PX dogs infused with either amino acids or glucagon (0.86 pmol/kg per min, i.v.) alone, RBF and GFR did not increase appreciably at baseline RAP. As RAP was reduced to 70 mmHg in these dogs, RBF and GFR remained at values that were greater than 90% of their respective controls. Yet, in PX dogs infused simultaneously with amino acids and glucagon, RBF and GFR rose by 22 and 24%, respectively, at baseline RAP. Moreover, as RAP was reduced to 70 mmHg, RBF and GFR fell by 22 and 31%, respectively. These data suggest that the ability of glucagon to modulate the renal hemodynamic response to amino acid infusion involves an impairment in renal autoregulation.

Amino Acids↗
PubMed1990

Effects of amino acid isomers on canine renal hemodynamics.

The major objective of this study was to ascertain whether the renal hemodynamic response to amino acid infusion in dogs is stereospecific. To test this hypothesis, we examined the renal hemodynamic effects of two isomers (L and D) of an amino acid mixture of serine, alanine, and proline (SAP; 0.051 mmol.kg-1.min-1) in anesthetized dogs. Intravenous infusion of L-SAP (n = 6) significantly elevated renal blood flow (RBF) and glomerular filtration rate (GFR) by 33 +/- 3 and 30 +/- 5%, respectively, over 1 h. DL-SAP (n = 6) elevated RBF and GFR by only 14 +/- 3 and 13 +/- 3%, respectively. Yet D-SAP (n = 6) failed to elevate either RBF or GFR over 1 h. Intravenous mannitol (940 mos-mol/kg; osmotic control; n = 6) also failed to elevate renal hemodynamics. In six other dogs, intrarenal infusion of L-, but not D-, SAP marginally elevated RBF and GFR by 13 +/- 2 and 12 +/- 2%, respectively, over 1 h. Infusion of alpha-aminoisobutyric acid (0.051 mmol.kg-1.min-1; n = 6), an amino acid analogue that is cotransported with sodium but not metabolized by renal cells, elevated RBF and GFR by 22 +/- 5 and 18 +/- 6%, respectively, over 1 h. These data indicate that vascular infusion of L, but not D, isomers of amino acids elevate RBF and GFR. We therefore suggest the importance of amino acid stereospecificity in the renal vascular response to amino acid infusion in dogs.

Alanine↗
PubMed1990

Renal vascular response to amino acids: effect of pancreatectomy.

We ascertained the importance of glucagon in modulating the renal hemodynamic response to amino acid (AA) infusion in anesthetized dogs. In controls (n = 6), AAs (L-serine, alanine, and proline; 0.051 mmol.kg-1.min-1 iv) elevated renal blood flow (RBF) and glomerular filtration rate (GFR) by 35 and 34%, respectively, while elevating arterial plasma glucagon-like immunoreactivity (AGLI) by 96 pmol/l. In control pancreatectomized (PX) dogs (n = 6), all parameters remained at control values over 2 h. In PX dogs, AAs (n = 6) failed to reproduce the renal hemodynamic and AGLI responses elicited by AAs in controls. In PX dogs infused with AAs, replacement of AGLI (n = 6) to an incremental plasma level of 111 pmol/l, a level no different than that produced by AAs in controls, elevated RBF and GFR by 25 and 26.5%, respectively. These hemodynamic responses were 71 and 78%, respectively, of the total responses elicited by AAs in controls. In PX dogs infused with glucagon alone (0.86 pmol.kg-1.min-1; n = 6), an incremental change in AGLI of 112 pmol/l was accompanied by only small increases in RBF and GFR (9%). These data suggest the importance of glucagon in modulating the renal hyperemia and hyperfiltration ascribed to AA infusion in anesthetized dogs.

Amino Acids↗
PubMed1989

Renal hemodynamic response to galanin: importance of elevated plasma glucose.

Although recent data point to a possible indirect role for galanin in modulating renal blood flow (RBF) and fluid homeostasis in experimental animals, there have been no systematic studies exploring the possible direct effects of the peptide on the mammalian kidney. We ascertained the RBF, glomerular filtration rate (GFR) and plasma glucose responses to direct intrarenal infusion of three progressively increasing doses of synthetic galanin in anesthetized dogs. A 50 ng/kg per min dose (n = 6) failed to affect RBF, GFR or arterial plasma glucose (APG). Yet, a 100 ng/kg per min dose elevated RBF and GFR by 13 and 14%, respectively, while concomitantly increasing APG by 38%. At 200 ng/kg per min, galanin elevated RBF and GFR by 32 and 33%, respectively, while elevating APG by 57%. Intrarenal infusion of glucose (12.5 mg/kg per min; n = 6), reproducing the percentage rise in glucose (62%) elicited by the highest dose of galanin, elevated RBF and GFR by 20 and 23%, respectively. These data indicate that the elevated plasma glucose level, stimulated by galanin infusion, may account for about 63 and 70% of the RBF and GFR responses, respectively, elicited by galanin infusion at the 200 ng dose. The factors mediating the remaining renal hyperemia and hyperfiltration await resolution.

Animals↗
PubMed1989

Nature of the renal hemodynamic action of amino acids in dogs.

Anesthetized dogs were used to study the nature of the renal hyperemia and hyperfiltration ascribed to amino acids. Intravenous (n = 6) or intraportal venous (n = 6) infusion of a solution of three metabolizable amino acids [serine, alanine, and proline (SAP) approximately 0.051 mmol.kg-1.min-1] elevated renal blood flow (RBF) and glomerular filtration rate (GFR) by a similar amount (30%) over the same time course (60 min). Yet, direct intra-arterial infusion of SAP into the kidney at either approximately 0.0051 or 0.051 mmol.kg-.min-1 (n = 12) failed to significantly elevate either RBF or GFR over 60 min. A transient increase in RBF (approximately 13%) was, however, noted by minute 15 of the infusion. Unlike SAP, intraportal venous infusion of a physiological dose of branched-chain amino acids (valine, leucine, and isoleucine, approximately 0.0195 mmol.kg-1.min-1, n = 6) failed to elevate either RBF or GFR over 60 min. By comparison, either intravenous or intraportal venous infusion of SAP at approximately 0.020 mmol.kg-1.min-1 (n = 12) elevated renal hemodynamics by approximately 14% over 60 min. The data suggest that the liver does not directly mediate amino acid-induced increases in renal hemodynamics but that some other intermediary step activated following amino acid administration may be necessary before the renal hyperemia and hyperfiltration ascribed to amino acids are manifested in anesthetized dogs.

Alanine↗
PubMed1988

Autoregulation of renal hemodynamics is not impaired by a 'physiologic' dose of glucagon.

Glucagon has been suggested to be involved in the pathway by which protein and amino acids elevate renal blood flow (RBF) and glomerular filtration rate (GFR) postprandially. Recent data suggest that amino acids elevate RBF and GFR through an autoregulatory mechanism (i.e., by impairing renal autoregulation). If glucagon mediates the renal hemodynamic effects of amino acids, 'physiologic' infusion of glucagon would also be expected to impair autoregulation. We examined the effects of glucagon (5 ng/kg per min given intraportally and intravenously) on RBF and GFR autoregulation in anesthetized dogs. Intraportal glucagon (n = 6) increased RBF (24%) and GFR (23%) at normal arterial pressure. RBF and GFR were well autoregulated (greater than 90% of control) at renal arterial pressures greater than or equal to 85 mm Hg before and after glucagon. At 70 mm Hg, RBF and GFR decreased by 15 and 16%, respectively, before glucagon and by 19 and 22%, respectively, after glucagon. Intravenous glucagon (n = 6) produced similar effects. Intraportal glucagon at 500 ng/kg per min increased RBF (35%), heart rate (69%) and plasma glucose (78%) and decreased arterial pressure (16%) (GFR not measured). This dose impaired RBF autoregulation by 30%. The data suggest that a 'physiologic' dose of glucagon increases renal hemodynamics without impairing renal autoregulation. It is suggested that glucagon's vasodilatory effect on the renal vasculature may be additive to the renal effects of amino acids.

Animals↗
PubMed1988

Potential mechanisms mediating postprandial renal hyperemia and hyperfiltration.

Although the existence of postprandial renal hyperemia and hyperfiltration has been established, the precise mechanism governing protein-mediated increases in renal hemodynamics is not, as yet, clearly defined. Investigative effort over the past decade has provided at least two plausible mechanisms playing an important role in renal hyperemia and hyperfiltration associated with ingestion of a protein-rich meal: 1) blood-borne vasoactive agents (e.g., pancreatic glucagon and/or hepatic glomerulopressin); and 2) intrarenal mechanisms (e.g., the tubuloglomerular feedback system). Data supporting each of these two candidate mechanisms are reviewed as are data supporting the importance of other factors such as renal prostanoids, the renin-angiotensin system, and renal cyclic nucleotides. It is anticipated that future investigative effort will be stimulated by our present knowledge of postprandial renal hemodynamics so that one day we not only will know the precise mechanisms governing postprandial renal hyperemia and hyperfiltration but, in addition, may gain valuable insight into the pathogenesis of chronic renal disease.

Animals↗
PubMed1987

Importance of collateral circulation in the vascularly occluded feline intestine.

The aim of this study was to assess the extent of collateral blood flow provided by the celiac and inferior mesenteric arteries to the intestines during total occlusion of the superior mesenteric artery (SMA). In anesthetized cats, blood flow to the pancreas, duodenum, jejunum, ileum, and colon was measured with radioactive micropheres (15 microns in diameter) before and during occlusion of the SMA. Superior mesenteric artery occlusion significantly decreased (by 63%) blood flow to the head of the pancreas. Flow to the neck and tail of the pancreas was not altered. Blood flow to the proximal and distal duodenum was significantly reduced by 35% and 61%, respectively. Along the entire jejunum and ileum, SMA occlusion markedly decreased blood flow by an average of 71%. In the proximal colon, blood flow decreased by 63%, whereas flow to the middle and distal colon was not affected by SMA occlusion. Reduction in total wall blood flow to the small and large intestines was largely due to a marked reduction in mucosa/submucosa blood flow; muscularis/serosa flow was not affected. The results of this study suggest that total occlusion of the SMA does not compromise blood flow to the neck and tail of the pancreas and middle and distal colon (tissues that are normally perfused with blood from either the celiac or inferior mesenteric arteries). Perfusion through collaterals maintains flow to the head of the pancreas and gut (from duodenum to proximal colon) to within 30%-65% of control (preocclusion) flow. An important new observation of this study is that collateral blood vessels are much more effective in preventing ischemia in the muscularis/serosa than in the mucosa/submucosa after SMA occlusion.

Animals↗
PubMed1987

Splanchnic and renal hemodynamic responses to intraportal infusion of glucagon.

We compared the 60-min splanchnic and renal hemodynamic responses to intraportal (IPV) and intravenous infusion of glucagon (5 ng.kg-1.min-1) in anesthetized dogs and quantitated the importance of glucose in mediating the renal hemodynamic responses to intraportal infusion of glucagon. Intraportal glucagon elevated superior mesenteric (SMA) and renal (RA) artery blood flows by 8 and 16%, respectively, by minute 15. By minute 30, RA flow had increased by 23%. Thereafter, SMA flow returned to control, while RA flow remained elevated by 24%. Glomerular filtration rate (GFR) followed the same pattern as RA flow over 60 min. Intravenous glucagon elicited smaller hemodynamic responses. During intraportal and intravenous glucagon infusion, plasma glucose rose by 20-25%. Renal hemodynamics were not affected by incremental changes in blood glucose of up to 6.25 mmol/l. At an incremental change in glucose of 10.06 mmol/l, RA flow and GFR were elevated by 12 and 9%, respectively. We conclude that intraportal glucagon infusion increases splanchnic and renal hemodynamics, although the splanchnic response is evanescent. Importantly, hepatic release of glucose into the circulation during intraportal glucagon infusion does not have a significant effect on renal hemodynamics. Thus, similar to intravenous infusion of the hormone, renal hemodynamic responses to intraportal glucagon are independent of and dissociated from elevations in blood glucose produced during hormone infusion.

Animals↗
PubMed1986

Renal hyperemia in portal hypertension is not mediated by gastrointestinal peptides.

The objectives of this study were to characterize the time course of development of the renal hyperemia induced by chronic portal vein stenosis (PVS) in the rat, and to assess the possibility that vasoactive blood-borne gastrointestinal peptides mediate the renal hyperemia in established portal hypertension. Blood flow to the kidneys was measured with radioactive microspheres over a ten day time course. On day 2, no difference in renal blood flow (RBF) was observed in PVS rats as compared with controls. However, by day 4, RBF significantly increased by 35% in PVS vs. control animals. On day 6, the renal hyperemia in PVS rats reached a maximal value that was 42% higher than controls. A steady state hyperemia (approximately 40%) was maintained thereafter. Radioimmunoassay of plasma from control and established portal hypertensive rats (10 days samples) revealed that vasoactive intestinal polypeptide, substance P, cholecystokinin, gastrin, neurotensin, pancreatic polypeptide, beta-endorphin and peptide histidine-isoleucine amide are not elevated in arterial plasma of portal hypertensive rats. These data suggest that the renal hyperemia induced by chronic portal vein stenosis is apparent within 4 days of the onset of a hypertensive state and attains a steady state by day 8. Furthermore, at least eight blood-borne gastrointestinal peptides are not directly involved in the renal hyperemia associated with chronic portal hypertension.

Animals↗
PubMed1986

Protein-mediated elevations in renal hemodynamics: existence of a hepato-renal axis?

Unlike the intestinal hyperemia which occurs following ingestion of a mixed meal, postprandial renal hemodynamic responses to food appear to be specific to protein-rich meals. Several observations have led to the proposal that following ingestion of protein (meat), a blood-borne factor(s) is released into the systemic circulation which elicits the increases in renal hemodynamics. Glucagon was initially considered as a prime hormonal candidate since the polypeptide is preferentially secreted by the endocrine pancreas in response to protein-rich meals and because glucagon elevates renal hemodynamics by selectively dilating renal afferent arterioles. However, recent data indicate that at postprandial blood levels, glucagon fails to directly mediate protein-induced renal hyperemia and hyperfiltration thus questioning the physiologic importance of glucagon on the renal vasculature. Data have accumulated indicating the importance of the liver and hepatic metabolism during protein-mediated elevations in renal hemodynamics. A hypothesis is advanced suggesting the existence and physiologic importance of a "hepato-renal axis" in mediating the postprandial increases in renal hemodynamics following ingestion of protein-rich meals. The blood-borne factor(s) mediating this response remains to be further clarified and defined.

Amino Acids↗
PubMed1986

Quantitative assessment of the two-component model of intestinal circulation.

Recently a two-component model of the intestinal circulation was proposed to explain the effects of vasodilators on intestinal oxygenation. This model assumes that the intestine is composed of two regions: one region in which oxygen uptake is blood flow independent (well perfused and normoxic) and a second region in which oxygen uptake is blood flow dependent (under-perfused and hypoxic). The model predicts that total intestinal oxygen uptake is increased by a vasodilator only if the blood flow-dependent region is affected. We used a systems analysis approach to predict the various boundary conditions that must be imposed on the two-component model for it to simulate experimental observations. The mathematical model was based on current concepts and available data regarding intestinal hemodynamics and oxygen exchange. The model simulations predict that 30-70% of the intestine must be hypoxic (regions where oxygen uptake is blood flow dependent) for the two-component hypothesis to adequately explain published observations. Since the existence of such an extensive hypoxic region seems unlikely for the normal intestine, the predictive value of the two-component hypothesis may be of limited value for describing the effects of vasodilators on oxygen uptake in the normal intestine. However, the two-component model may be useful in predicting the effects of vasodilators on intestinal oxygen uptake in the ischemic intestine.

Blood Flow Velocity↗
PubMed1986

Role of glucagon in splanchnic hyperemia of chronic portal hypertension.

The role of glucagon as a blood-borne mediator of the hyperdynamic circulation associated with chronic portal venous hypertension was assessed in the rat portal vein stenosis model. Selective removal of pancreatic glucagon from the circulation was achieved by intravenous infusion of a highly specific glucagon antiserum. Blood flow to splanchnic organs, kidneys, and testicles was measured with radioactive microspheres, and the reference-sample method. Glucagon antiserum had no effect on blood flow in the gastrointestinal tract of sham-operated (control) rats. However, the antiserum produced a significant reduction in hepatic arterial blood flow in the control rats, suggesting that glucagon contributes significantly to the basal tone of hepatic arterioles. In portal hypertensive rats glucagon antiserum significantly reduced blood flow to the stomach (22%), duodenum (25%), jejunum (24%), ileum (26%), cecum (27%), and colon (26%). Portal venous blood flow was reduced by approximately 30%. The results of this study support the hypothesis that glucagon mediates a portion of the splanchnic hyperemia associated with chronic portal hypertension.

Animals↗
PubMed1985

Postprandial regulation of intestinal blood flow: role of gastrointestinal hormones.

Systemic arterial pressure, jejunal perfusion pressure, and jejunal blood flow were measured in eight autoperfused canine jejunum preparations (5 dogs) before and during local intra-arterial infusion of physiological doses of secretin (18.5 pM), neurotensin (233 pM), and cholecystokinin octapeptide (CCK-8, 30 pM). Intra-arterial infusion of secretin, neurotensin, or CCK-8 alone did not affect either systemic or jejunal arterial pressures. Likewise, jejunal blood flow was not significantly altered by secretin (3 +/- 3%), neurotensin (-5 +/- 4%), or CCK-8 (-5 +/- 5%). Even when all three hormones were infused simultaneously, jejunal blood flow was not altered (2 +/- 3%). However, when infused at rates that produced calculated arterial blood levels some 100 times greater than those reported as "postprandial," each hormone alone, as well as in combination, produced marked increases in jejunal blood flow. Secretin, neurotensin, and CCK-8 increased blood flow by 34 +/- 8, 31 +/- 11, and 24 +/- 5%, respectively. Simultaneous infusion of all three hormones increased jejunal blood flow by 47 +/- 11%. These data suggest that, either alone or in combination, secretin, neurotensin, and CCK-8 are not of quantitative importance in regulating jejunal blood flow during the postprandial state. However, higher (presumably pharmacological) blood levels of these hormones do significantly elevate jejunal blood flow.

Animals↗