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D L Mattson

Publications and source records attributed to D L Mattson.

At least 37 records · Page 2Linked to original sources
PubMed1997

Localization of the vasopressin V1a and V2 receptors within the renal cortical and medullary circulation.

Arginine vasopressin (AVP) is a potent vasoconstrictor that preferentially reduces renal medullary blood flow through the stimulation of the vasopressin V1a receptor (V1aR). Studies have also shown that the vasopressin V2 receptor (V2R) may modulate AVP-mediated vasoconstriction. At present, the distribution of the V1aR and V2R within the renal cortical and medullary microcirculation has not been determined. This study was designed to localize the transcriptional and translational sites of the V1aR and V2R in microdissected intrarenal vascular segments from both the cortex and medulla, specifically the interlobar, arcuate, and interlobular arteries; afferent and efferent arterioles; glomeruli; and single outer medullary vasa recta capillaries using reverse transcription-polymerase chain reaction and Western blot analyses. The results indicated that V1aR mRNA and proteins were present in the isolated cortical or medullary vasculature, but the V2R mRNA and proteins were not found. This study suggests that the vasoconstrictor action of AVP within the renal medulla is mediated through the V1aR and that the modulatory V2R-mediated vasodilation is probably through the release of paracrine hormones found within the renal interstitial or tubular cells.

Animals↗
PubMed1997

Evidence for the presence of smooth muscle alpha-actin within pericytes of the renal medulla.

This study was designed to determine whether smooth muscle alpha-actin mRNA and smooth muscle alpha-actin contractile protein elements were present within the renal medullary pericytes. Extraction of total RNA from microdissected outer medullary descending vasa recta allowed for the detection of smooth muscle alpha-actin mRNA expression using reverse transcription-polymerase chain reaction (RT-PCR). Expression of smooth muscle alpha-actin was specific to the descending vasa recta and not a result of tubular contamination because RT-PCR amplification of the vasopressin V2 receptor, which is a specific tubular marker, did not occur. To determine the exact cell type(s) that translate the mRNA into protein, we performed immunohistochemistry on the renal outer and inner medulla using a monoclonal smooth muscle alpha-actin antibody, whose specificity was determined by immunoblot analysis. Smooth muscle alpha-actin protein was found selectively within the pericytes surrounding the descending vasa recta from the outer and inner medullary tissue sections. This study demonstrates that the pericytes alone that surround the descending vasa recta within the outer and inner medulla contain smooth muscle alpha-actin mRNA and protein and are therefore the site of the contractile elements that could play a vasomodulatory role in the control of renal medullary blood flow and its distribution within the renal medulla.

Actins↗
PubMed1997

Inhibition of renal outer medullary 20-HETE production produces hypertension in Lewis rats.

Recent studies have indicated that a deficiency in the production of 20-hydroxyeicosatetraenoic acid (20-HETE) in the outer medulla of the kidney may contribute to the abnormalities in the renal handling of sodium and the development of hypertension in Dahl salt-sensitive rats. To determine whether a reduction in 20-HETE production in the outer medulla is sufficient to induce hypertension, an inhibitor of the renal metabolism of arachidonic acid by P450 enzymes, 17-octadecenoic acid (17-ODYA), was chronically infused directly into the outer medulla of the left kidney of uninephrectomized Lewis rats fed a high salt diet. Renal medullary interstitial infusion of 17-ODYA (400 pmol/min) reduced the formation of 20-HETE in the outer medulla of the infused kidney by 70% compared with values seen in the right kidney collected when the rat was uninephrectomized, but it had no effect on the production of 20-HETE in the renal cortex. After 5 days, mean arterial pressure rose from 115 +/- 2 to 142 +/- 2 mm Hg (n = 6) in the rats infused with 17-ODYA, while mean arterial pressure was not significantly altered in the rats infused with vehicle alone (116 +/- 1 versus 117 +/- 2 mm Hg, n = 6). These results suggest that inhibition of the renal metabolism of arachidonic acid by P450 enzymes in the outer medulla of the kidney is sufficient to induce the development of hypertension in Lewis rats fed a high salt diet and support the view that P450 metabolites of arachidonic acid play an important role in the regulation of renal function and the long-term control of arterial pressure.

Animals↗
PubMed1996

Influence of dietary sodium intake on renal medullary nitric oxide synthase.

We previously reported that chronic systemic treatment of rats with a nitric oxide synthase inhibitor leads to a selective decrease in renal medullary blood flow, retention of sodium, and the development of hypertension. In the present studies, we used protein blotting techniques to determine the whole tissue distribution and relative quantitation of the different nitric oxide synthase isoforms in the renal cortex and medulla of Sprague-Dawley rats maintained on a low (0.4% NaCl) or high (4.0% NaCl) dietary salt intake. Neural, endothelial, and inducible nitric oxide synthase were readily detectable in homogenized renal inner and outer medullas. Only endothelial nitric oxide synthase was detectable in the renal cortex. Densitometric comparison of Western blots from equal amounts of total inner medullary tissue protein indicated that endothelial, inducible, and neural nitric oxide synthase were increased by 145%, 49%, and 119%, respectively, in rats maintained on a high NaCl diet compared with rats on a low NaCl diet. No significant differences in nitric oxide synthase levels were detected in the outer medulla, renal cortex, or aorta of rats maintained on low and high NaCl diets. In separate studies, continuous intravenous infusion of N(G)-nitro-L-arginine methyl ester (8.6 mg/kg per day) for 11 days in chronically instrumented rats increased mean arterial pressure 32 +/- 3 mm Hg in rats on a high NaCl diet (n=5) but only increased pressure 17 +/- 3 mm Hg in rats on a low NaCl diet (n=6). These data indicate that increased levels of renal medullary nitric oxide synthase may be important in the chronic adaptation to increased sodium intake.

Animals↗
PubMed1996

Neural nitric oxide synthase in the renal medulla and blood pressure regulation.

We studied the effect of selective inhibition of the neural isoform of nitric oxide synthase in the rat renal medulla in conscious Sprague-Dawley rats. Continuous renal medullar interstitial infusion of an antisense oligonucleotide complementary to the initiation region of the mRNA for neural nitric oxide synthase increased blood pressure 14 +/- 1 mm Hg in rats maintained on a high sodium intake. Medullary interstitial infusion of saline vehicle or a scrambled oligonucleotide probe failed to alter blood pressure in separate groups of high salt control rats. Renal medullary interstitial infusion of the antisense oligonucleotide significantly decreased the level of neural nitric oxide synthase in the renal medulla by 53 +/- 8% and decreased total renal medullary nitric oxide synthase activity by 28 +/- 8%. No alterations were detected in the levels of inducible nitric oxide synthase or beta-actin in the antisense oligonucleotide-infused rats. To confirm the antisense oligonucleotide data, we administered a mechanistically different inhibitor of neural nitric oxide synthase, 7-nitroindazole, to an additional group of rats maintained on a high salt diet. Direct renal medullary interstitial infusion of this selective enzyme inhibitor significantly increased mean arterial pressure (15 +/- 6 mm Hg) and decreased total renal medullary nitric oxide synthase activity by 37 +/- 12% in rats on a high sodium diet. The present experiments demonstrate a role for the neural isoform of nitric oxide synthase in the long-term control of blood pressure in the presence of a high salt diet.

Animals↗
PubMed1995

Role of changes in renal hemodynamics and P-450 metabolites of arachidonic acid in the reversal of one-kidney, one clip hypertension.

OBJECTIVE: To examine the role of changes in renal hemodynamics and P-450 metabolites of arachidonic acid in the reversal of one-kidney, one clip (1-K,1C) hypertension in rats. DESIGN: The stimulus for the release of an antihypertensive lipid from the kidney is not known. This study examined whether cortical or papillary blood flow is altered after removal of the clip from the renal artery of 1-K,1C hypertensive rats, and the effects of blockade of the renal metabolism of arachidonic acid by P-450 with 17-octadecynoic acid (17-ODYA) on the fall in blood pressure. METHODS: Cortical and medullary blood flows were measured using laser-Doppler flowmetry. 17-ODYA (33 nmol/min) was infused directly into the renal artery to examine the effect of inhibition of renal P-450 activity on reversal of 1-K,1C hypertension. The renal metabolism of arachidonic acid in control and in 1-K,1C hypertensive rats was assessed by incubating microsomes with [14C]-arachidonic acid, the metabolites formed being measured using reverse-phase high-performance liquid chromatography. The antihypertensive effects of these P-450 metabolites of arachidonic acid were compared with those of medullipin I after intravenous administration in conscious spontaneously hypertensive rats (SHR). RESULTS: Cortical and papillary blood flow increased significantly and arterial pressure fell after unclipping the renal artery in the 1-K,1C hypertensive rats. 17-ODYA prevented the fall in blood pressure after unclipping. The production of epoxy- and dihydroxy-eicosatrienoic acids was elevated in microsomes prepared from the renal cortex of the 1-K,1C hypertensive rats. However, intravenous administration of these metabolites did not mimic the effect of medullipin I to lower arterial pressure in SHR. CONCLUSION: Elevations in renal cortical or papillary blood flow, or both, may stimulate the release of a P-450-derived antihypertensive lipid from the kidney after unclipping of the renal artery in 1-K,1C hypertensive rats. However, it is unlikely that this substance is a P-450 metabolite of arachidonic acid.

Animals↗
PubMed1995

Role of renal medullary blood flow in the development of L-NAME hypertension in rats.

The effect of chronic intravenous infusion of the nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 8.6 mg.kg-1.day-1) on blood pressure, intrarenal blood flow distribution, and sodium and water balance was studied in conscious rats. On the 1st day of intravenous L-NAME infusion, renal medullary blood flow was reduced by 22%, renal cortical blood flow was unaltered, approximately 1 meq of sodium and 12 ml of water were retained, and blood pressure increased from 96 +/- 2 to 118 +/- 2 mmHg. Medullary blood flow was maintained at this decreased level, sodium continued to be retained, body weight continued to increase, and blood pressure remained elevated for the 5 days of L-NAME infusion. During the postcontrol period, blood flow in the renal medulla returned to levels not significantly different from control; the animals went into negative sodium balance and stopped gaining weight, and blood pressure returned to control. The present experiments indicate that decreased renal medullary blood flow and retention of sodium and water play an important role in the development of hypertension during chronic systemic L-NAME administration despite no measurable changes in renal cortical blood flow.

Acetylcholine↗
PubMed1995

In vivo diuretic actions of renal vasopressin V1 receptor stimulation in rats.

The specific vasopressin V1 receptor agonist (V1AG; [Phe2,Ile3,Orn8]vasopressin) was infused (2.0 ng.kg-1.min-1) into the renal medullary interstitial space to determine the effects of selective medullary V1 receptor stimulation on sodium and water excretion in normal rats. Responses were compared with those of arginine vasopressin (AVP) and vasopressin V2 receptor stimulation resulting from infusion of a V1 receptor antagonist with AVP. Medullary infusion of V1AG or AVP in euvolemic rats produced no changes in hemodynamics or glomerular filtration rate. V1AG increased urine flow > 60% in euvolemic rats, whereas no change was observed with AVP. This response could not be explained by a rise of arterial pressure or by volume retention. With V2 stimulation in euvolemic rats, urine flow was decreased. In water diuretic rats, V1AG produced no change, whereas AVP infusion decreased urine flow. The results provide in vivo evidence that tubular V1 vasopressin receptor activity results in increased urine flow and thereby modulates the antidiuretic actions of vasopressin in the euvolemic state.

Animals↗
PubMed1995

Control of renal medullary blood flow by vasopressin V1 and V2 receptors.

Experiments were performed in anesthetized renal-denervated rats to determine the contribution of renal medullary vasopressin V1 and V2 receptor stimulation in the regulation of renal medullary blood flow. Renal medullary interstitial infusion of the selective V1 agonist [Phe2,Ile3,Orn8]vasopressin (2 ng.kg-1.min-1) significantly decreased outer medullary blood flow by 15% and inner medullary blood flow by 35%, as measured with implanted optical fibers for laser-Doppler flowmetry. Medullary interstitial infusion of equimolar doses of arginine vasopressin (AVP) also decreased outer medullary blood flow by 15% but decreased inner medullary blood flow by only 17%, a decrease significantly less than that during the infusion of the V1 agonist. These results were confirmed in videomicroscopy experiments on the exposed papilla, which demonstrated that the V1 agonist and AVP decreased descending and ascending vasa recta capillary red blood cell velocity and calculated blood flow, with greater decreases during infusion of the V1 agonist. In further laser-Doppler flowmetry studies, stimulation of V2 receptors by medullary interstitial infusion of 1-desamino-8-D-arginine vasopressin (2 ng.kg-1.min-1) or AVP in rats pretreated with the vasopressin V1 receptor antagonist d(CH2)5[Tyr(Me)2,Ala-NH2]AVP increased renal medullary blood flow by 16 +/- 3 and 27 +/- 8%, respectively. The present experiments indicate that vasopressin V1 receptor stimulation serves to decrease renal medullary blood flow while V2 receptor stimulation appears to increase renal medullary blood flow; however, the net effect of AVP is to decrease renal medullary blood flow.

Animals↗
PubMed1995

The renal medulla and hypertension.

We review evidence supporting the conclusion that renal dysfunction underlies the development of all forms of hypertension in humans and experimental animals. Indexes of global renal function are generally normal in the early stages of most genetic forms of hypertension, but renal function is clearly impaired in long-established hypertension. Studies in our laboratory over the past decade summarized below have established that the renal medulla plays an important role in sodium and water homeostasis and in the long-term control of arterial pressure. Development of implanted optical fibers for measurement of cortical and medullary blood flows with laser-Doppler flowmetry and techniques for delivery of vasoactive compounds into the medullary interstitial space enabled us to examine determinants of medullary flow (nitric oxide, atrial natriuretic peptides, kinins, eicosanoids, vasopressin, renal sympathetic nerves, etc). We have shown in spontaneously hypertensive rats that the initial changes of renal function begin as a reduction of medullary blood flow in the absence of changes of cortical flow. Long-term medullary interstitial infusion of captopril, which preferentially increased medullary blood flow, resulted in a lowering of arterial pressure. In normal Sprague-Dawley rats, selective reduction of medullary flow with medullary interstitial or intravenous infusion of small amounts of NG-nitro-L-arginine methyl ester resulted in hypertension. These and other studies we review show that although blood flow to the inner renal medulla comprises less than 1% of the total renal blood flow, changes in flow to this region can have a major effect on sodium and water homeostasis and on the long-term control of arterial blood pressure.

Animals↗
PubMed1994

Effect of chronic renal medullary nitric oxide inhibition on blood pressure.

The effects of chronic nitric oxide inhibition in the renal medulla on renal cortical and medullary blood flow, sodium balance, and blood pressure were evaluated in conscious uninephrectomized Sprague-Dawley rats. During a 5-day renal medullary interstitial infusion of the nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 120 micrograms/h) in saline (0.5 ml/min), renal medullary blood flow was selectively decreased by 30% after 2 h and was maintained at that level for the entire infusion. The decrease in medullary blood flow was associated with sodium retention and increased blood pressure. After the cessation of L-NAME infusion, medullary blood flow returned to control, and the sodium balance became negative as blood pressure returned to baseline. These data indicate that renal medullary nitric oxide plays an important role in the regulation of renal blood flow, sodium excretion, and blood pressure.

Animals↗
PubMed1994

Renal medullary captopril delivery lowers blood pressure in spontaneously hypertensive rats.

We examined the contribution of renal medullary function to the maintenance of hypertension in spontaneously hypertensive rats by infusing captopril chronically into the renal medullary interstitial space of uninephrectomized rats. Changes in cortical and medullary blood flow were determined using a newly developed optical fiber implantation technique for laser-Doppler flowmetry. Renal medullary interstitial infusion of captopril (5 mg/kg per day) selectively increased medullary blood flow by 40% without altering renal cortical blood flow throughout the 5 days of captopril delivery. In association with the selective increase of medullary perfusion, a significant natriuresis was observed on the second day of the drug infusion, and urine osmolality was significantly reduced during the first 3 days of captopril infusion. Mean arterial pressure was significantly decreased by 20 mm Hg during 5 days of captopril infusion, and the chronic renal function curve was shifted to a lower level of arterial pressure compared with the control values when 0.9% sodium chloride saline vehicle was infused. Intravenously infused captopril at 5 mg/kg per day did not alter mean arterial pressure, excluding the possibility that the hypotensive effect of medullary captopril infusion was due to recirculation. In summary, chronic reduction of the elevated renal medullary vascular tone by medullary interstitial infusion of captopril reset the steady-state renal function curve and lowered arterial pressure in spontaneously hypertensive rats.

Animals↗
PubMed1993

Relationship between renal perfusion pressure and blood flow in different regions of the kidney.

The present study examined the autoregulation of blood flow in different regions of the renal cortex and medulla in volume-expanded or hydropenic anesthetized rats. Blood flow was measured in the whole kidney by electromagnetic flowmetry, in the superficial cortex with implanted fibers and external probes for laser-Doppler flowmetry, and in the deep cortex and inner and outer medulla with implanted fibers for laser-Doppler flowmetry. At renal perfusion pressure > 100 mmHg, renal blood flow, superficial cortical blood flow, and deep cortical blood flow were all very well autoregulated in both volume-expanded and hydropenic rats. Inner and outer medullary blood flow were also well autoregulated in hydropenia, but blood flow in these regions was very poorly autoregulated in volume-expanded animals. As renal perfusion pressure was decreased below 100 mmHg in volume-expanded and hydropenic animals, renal blood flow, superficial and deep cortical blood flow, and inner and outer medullary blood flow all decreased. The results of these experiments demonstrate that blood flow in both the inner and outer portions of the renal medulla of the kidney is poorly autoregulated in volume-expanded rats but well autoregulated in hydropenic animals. In contrast, blood flow in all regions of the renal cortex is well autoregulated in both volume-expanded and hydropenic animals. These results suggest that changes in resistance in the postglomerular circulation of deep nephrons are responsible for the poor autoregulation of medullary blood flow in volume expansion despite well autoregulated cortical blood flow.

Animals↗
PubMed1993

Assessment of changes in intrarenal blood flow in conscious rats using laser-Doppler flowmetry.

The present study was designed to develop, for the first time, a method that allows long-term repeated measurements of renal cortical blood flow (CBF) and medullary blood flow (MBF) in conscious unanesthetized rats. The use of fiber-optic probes (0.5 mm diam) for the chronic measurement of renal CBF and MBF was evaluated. Basal renal cortical and medullary laser-Doppler flow (LDF) signals and the responses to intravenous bolus injections of angiotensin II (ANG II, 12.5 ng) were determined every other day for 11 days in conscious Sprague-Dawley rats (n = 9). A recovery period of 5-7 days after surgery was required before stable signals were obtained from the implanted probes. Thereafter, the fiber-optic probes gave reproducible laser-Doppler measurements of CBF and MBF for 11 days. The CBF and MBF responses to intravenous bolus injections of ANG II (12.5 ng) were also constant during this period. Chronic implantation of the fiber-optic probes caused minimal tissue damage and did not significantly alter urine concentrating ability or renal function. These findings suggest that LDF technique with chronically implanted optical fibers provides a new tool for the continuous long-term monitoring of regional blood flow in the kidney of conscious rats.

Angiotensin II↗
PubMed1993

Kinin actions on renal papillary blood flow and sodium excretion.

Infusion of bradykinin into the renal medullary interstitium (0.1 micrograms/min, n = 6) significantly increased renal papillary blood flow as measured by laser-Doppler flowmetry to 117 +/- 3% of control without altering cortical blood flow or blood pressure in anesthetized Munich-Wistar rats. In animals prepared for clearance studies, renal medullary bradykinin infusion did not alter total renal blood flow, glomerular filtration rate, or renal interstitial hydrostatic pressure but increased urine flow by 100%, sodium excretion by 111%, and fractional sodium excretion by 107%. No changes occurred in mean arterial pressure or contralateral kidney function during the interstitial bradykinin infusion. Blockade of endogenous kinin degradation by interstitial infusion of captopril (1 mg/hr) significantly increased papillary blood flow by 21 +/- 5% without altering cortical blood flow. Pretreatment with the nitric oxide inhibitor NG-nitro-L-arginine-methyl ester (2 micrograms/min, n = 7) eliminated the increase in papillary blood flow associated with either bradykinin or captopril infusion. We conclude that renal medullary interstitial infusion of bradykinin increases sodium and water excretion, which is associated with a selective increase in papillary blood flow by a nitric oxide-dependent mechanism.

Animals↗
PubMed1992

Renal medullary interstitial infusion of diltiazem alters sodium and water excretion in rats.

The role of renal papillary blood flow in regulation of fluid and electrolyte excretion was examined. The effects of an acute infusion of diltiazem (5 micrograms.kg-1 x min-1) into the renal medullary interstitium on papillary blood flow and sodium and water excretion were studied. Changes of renal blood flow were measured using an electromagnetic flow probe. Cortical and papillary blood flows were measured using laser-Doppler flowmetry. Renal and cortical blood flows were unchanged during medullary interstitial infusion of diltiazem, but papillary blood flow increased 26% (P < 0.05) and remained elevated for 1 h after diltiazem infusion was discontinued. Glomerular filtration rate (GFR) of the infused kidney increased by 21% from a control of 1.0 +/- 0.1 ml.min-1 x g-1 during infusion of diltiazem (P < 0.05), but it returned to control after diltiazem infusion was stopped. Urine flow and sodium excretion increased by 70% (P < 0.05), and fractional sodium excretion rose from 1.5 +/- 0.2 to 2.4 +/- 0.3% of the filtered load during the hour after diltiazem infusion. Renal blood flow, cortical and papillary blood flow, GFR, urine flow, and sodium excretion in the 0.9% sodium chloride vehicle-infused kidney were not significantly altered during the experiment. Intravenous infusion of the same dose of diltiazem (5 micrograms.kg-1 x min-1) increased GFR by 22%, but had no effect on urine flow and sodium excretion. These results indicate that renal medullary interstitial infusion of diltiazem selectively increased renal papillary blood flow, which was associated with an increase of sodium and water excretion.

Animals↗
PubMed1992

Role of nitric oxide in renal papillary blood flow and sodium excretion.

Renal medullary interstitial infusion of NG-nitro-L-arginine (120 micrograms/hr, n = 7) decreased papillary blood flow to 71 +/- 5% of control without altering outer cortical flow. Before NG-nitro-L-arginine infusion, interstitial acetylcholine administration (200 micrograms/hr) increased cortical and papillary blood flow to 134 +/- 6% and 113 +/- 2% of control, respectively. After NG-nitro-L-arginine administration, the vasodilator response to acetylcholine was abolished. In clearance experiments, renal medullary infusion of NG-nitro-L-arginine (120 micrograms/hr, n = 7) significantly decreased total renal blood flow by 10%, renal interstitial fluid pressure by 23%, sodium excretion by 34%, and urine flow by 39% without altering glomerular filtration rate, fractional sodium and water excretion, blood pressure, or urine osmolality. These data indicate that selective inhibition of nitric oxide in the renal medullary vasculature reduces papillary blood flow, which is associated with decreased sodium and water excretion. We conclude that nitric oxide exerts a tonic influence on the renal medullary circulation.

Animals↗