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L M Harrison-Bernard

Publications and source records attributed to L M Harrison-Bernard.

17 recordsLinked to original sources
PubMed2000

Renal responses to AT1 receptor blockade.

Because of the importance of the renin-angiotensin system in the pathophysiology of hypertension and in mediating associated alterations in renal function, angiotensin II (Ang II) AT1 receptor blockers provide a direct means of protecting against influences of excessive Ang II levels. The kidney is an important site of action of Ang II AT1 receptor blockers because intrarenal Ang II not only vasoconstricts the renal vasculature but also reduces sodium excretion and suppresses the pressure natriuresis relationship. Even in normal conditions, intrarenal Ang II content is greater than can be explained on the basis of circulating Ang II and is compartmentalized with proximal tubule concentrations of Ang I and Ang II being several times higher than plasma concentrations. The localization of angiotensinogen in proximal tubule cells further supports the concept that the proximal tubule secretes Ang II or precursors of Ang II into the tubular fluid to activate luminal Ang II receptors. Recent immunohistochemical studies have demonstrated an abundance of AT1 receptors on the luminal surface of proximal and distal tubule cells as well as on vascular smooth muscle cells of afferent and efferent arterioles and on glomerular mesangial cells. Activation of luminal AT1 receptors stimulates the sodium hydrogen exchanger and increases reabsorption rate. The prominence of AT1 receptors in vascular and epithelial tissues in the kidney provides the basis for the powerful effects of AT1 receptor blockers on renal function especially in hypertensive conditions. In the two-kidney, one-clip (2K1C) Goldblatt hypertensive rat model, the nonclipped kidney is renin depleted but the intrarenal Ang II levels are not suppressed and Ang II concentrations in proximal tubular fluid remain high (10(-8) mol/L). AT1 receptor blockers such as candesartan have been shown to cause significant increases in glomerular filtration rate, renal blood flow and proportionately much greater increases in sodium excretion and fractional sodium excretion. Ang II blockade also markedly increases the slope of the pressure natriuresis relationship. The collective actions of Ang II blockers on tubular transport and renal hemodynamics provide long-term effects to regulate sodium balance, which contributes to the long-term control of hypertension.

Angiotensin Receptor Antagonists↗
PubMed1999

Regulation of angiotensin II type 1 receptor mRNA and protein in angiotensin II-induced hypertension.

Chronic elevations of circulating angiotensin II (Ang II) cause sustained hypertension and enhanced accumulation of intrarenal Ang II by an AT1 receptor-dependent process. The present study tested the hypothesis that chronic elevations in circulating Ang II regulate AT1 mRNA and protein expression in a tissue-specific manner. Sprague-Dawley rats were infused with Ang II (80 ng/min) or vehicle subcutaneously for 13 days via osmotic minipump. On day 12, systolic blood pressure averaged 186+/-12 mm Hg in Ang II-infused rats compared with rats given vehicle (121+/-2 mm Hg). Plasma renin activity was markedly suppressed in the Ang II-infused rats compared with vehicle-infused rats (0.1+/-0.01 versus 4.9+/-0.9 ng of Ang I. mL-1. h-1; P<0.05). Semiquantitative reverse transcription polymerase chain reaction using rat AT1A- and glyceraldehyde-3-phosphate-dehydrogenase (GAPDH)-specific primers was followed by Southern blot hybridization using specific radiolabeled cDNA or oligonucleotide probes. The results showed that the ratios of AT1A/GAPDH mRNA in the kidney (0.19+/-0.05 versus 0. 26+/-0.03) and liver (2.8+/-0.9 versus 3.0+/-0.5) were comparable in Ang II- and vehicle-infused rats. In contrast, AT1A/GAPDH mRNA levels were increased in the adrenal glands of Ang II-infused rats (0.49+/-0.04 versus 0.36+/-0.02; P<0.05). Western blot analysis showed that AT1 protein levels in the kidney and liver were also similar in the two groups. Therefore, these results indicate that renal and liver AT1 receptor gene expression is maintained in Ang II-induced hypertension. The failure to downregulate AT1 receptor mRNA and protein levels thus allows the sustained effects of chronic elevations in Ang II to elicit progressive increases in arterial pressure.

Angiotensin I↗
PubMed1999

Early onset salt-sensitive hypertension in bradykinin B(2) receptor null mice.

Kinins have been implicated in the hemodynamic adaptation to postnatal life. The present study examined the impact of bradykinin B(2) receptor (B(2)R) gene disruption on the postnatal changes in blood pressure (BP) and the susceptibility to early onset salt-sensitive hypertension in mice. B(2)R null (-/-) and wild-type (+/+) mice were fed normal (NS, 1% NaCl) or high (HS, 5% NaCl) salt diets during pregnancy. After birth, the pups remained with their mothers until they were weaned and were subsequently continued on the respective maternal salt intake until 4 months of age. The age-related changes at 3 and 4 months in tail-cuff BP and anesthetized mean arterial pressure at 4 months were not different in NS/B(2)R(-/-) and NS/B(2)R(+/+) mice. However, there was a mild increase in BP in NS/B(2)R(-/-) at 2 months versus NS/B(2)R(+/+). In contrast, HS/B(2)R(-/-) mice manifested early onset and persistent elevations of tail-cuff BP (P<0.05) at 2, 3, and 4 months versus other groups. MAP was also higher in HS/B(2)R(-/-) than HS/B(2)R(+/+), NS/B(2)R(-/-), and NS/B(2)R(+/+) (91+/-3 versus 75+/-5, 74+/-2, and 70+/-2 mm Hg, respectively; P<0.05). Kidney renin and angiotensin type 1 receptor mRNA levels were not different. Additional studies showed that a delay in the initiation of HS until after birth was accompanied by later development of hypertension, although postnatal discontinuation of HS resulted in a gradual return of BP to normal values by 4 months of age. The results demonstrate that (1) kinins protect the developing animal from salt-sensitive hypertension, (2) lack of B(2)R from early development does not alter the maturation of BP under conditions of normal sodium intake, and (3) exposure to a HS diet during fetal life is not sufficient in itself to induce long-term hypertension in either wild-type or B(2)R null mice.

Age Factors↗
PubMed1999

Intrarenal angiotensin II generation and renal effects of AT1 receptor blockade.

The intrarenal renin-angiotensin system plays a critical role in the paracrine regulation of renal function and the pathophysiology of hypertension. Angiotensin II (AngII) is formed intrarenally from systemically delivered angiotensin I (AngI) and intrarenally formed AngI. Intrarenal AngII content, which is greater than can be explained by the circulating AngII concentrations, is compartmentalized such that proximal tubule concentrations of AngI and AngII greatly exceed plasma concentrations. Proximal tubule cells are thought to secrete AngII or precursors of AngII into the tubular fluid to activate luminal AngII receptors. Recent immunohistochemical studies have demonstrated an abundance of AT1 receptors on the luminal surface of proximal and distal tubule cells and on afferent and efferent arteriolar vascular smooth muscle cells and mesangial cells of glomeruli. Activation of luminal AT1 receptors stimulates tubular sodium reabsorption rate. To evaluate the direct effects of AT1 receptor blockade on renal function in AngII-dependent hypertension, experiments were performed on two-kidney, one-clip (2K1C) Goldblatt hypertensive rats. Although the nonclipped kidney is renin-depleted, the intrarenal AngII levels are not suppressed, and AngII concentrations in proximal tubular fluid remain high (10(-8) M). Candesartan was administered into the renal artery of nonclipped kidneys to avoid the confounding consequences of decreases in arterial pressure. Blockade of intrarenal AT1 receptors elicited significant increases in GFR, renal blood flow, sodium excretion, and fractional sodium excretion, suggesting synergistic actions on tubular transport and vascular smooth muscle cells.

Angiotensin I↗
PubMed1999

Concentrations and actions of intraluminal angiotensin II.

Although the presence of angiotensin II (AngII) receptors on the luminal membranes of proximal tubule cells has been recognized for many years, recent immunohistochemical studies using polyclonal and monoclonal antibodies to the AngII type 1 (AT1) receptor have demonstrated an abundance of the AT1 receptor not only on the luminal surface of proximal tubule cells but also on the luminal surfaces of distal nephron segments. An important role for these receptors in the regulation of tubular transport mechanisms was indicated by the recent findings of remarkably high proximal intratubular concentrations of AngII (in the range of 10(-9) to 10(-8) M). The high intratubular concentrations of AngII, as well as angiotensin I and angiotensinogen, are much greater than can be explained on the basis of delivery via glomerular filtration. When coupled with the findings demonstrating the presence of angiotensinogen and angiotensinogen mRNA in proximal tubule cells, the data indicate that AngII or precursors of AngII are secreted directly into the proximal tubule lumen by the epithelial cells. Although the mechanisms responsible for the regulation of intratubular AngII concentrations remain to be determined, micropuncture studies have provided direct evidence that activation of intraluminal AT1 receptors by AngII exerts a substantial stimulatory influence on sodium and bicarbonate transport by both proximal and distal tubules. Collectively, these data provide support for the hypothesis that activation of luminal AT1 receptors by AngII present in the tubular fluid contributes importantly to regulation of the tubular reabsorption rate.

Angiotensin II↗
PubMed1997

Immunohistochemical localization of ANG II AT1 receptor in adult rat kidney using a monoclonal antibody.

Molecular and functional studies have suggested that AT1 receptors are present in most nephron segments, yet direct demonstration of AT1 at these sites is lacking. The present study was performed to determine the intrarenal localization of the AT1 receptor utilizing a monoclonal anti-peptide (amino acid residues 8-17) antibody (6313/G2) in adult male Sprague-Dawley rats. Western blot analysis of kidney protein extracts showed a predominant 41-kDa immunoreactive band corresponding to the molecular weight of the deduced cDNA sequence. To determine optimal fixation conditions, kidney tissues were immersion fixed in Bouin's solution, 10% buffered Formalin, or 4% paraformaldehyde. Specificity of immunostaining was documented by preadsorption of the antibody with the immunogenic peptide sequence. Prominent AT1 immunostaining was visualized in the proximal tubule brush-border and basolateral membranes. In addition, distal tubules, cortical and medullary collecting ducts, and the renal arterial vasculature exhibited specific immunoreactivity. Glomerular staining for AT1 was observed in mesangial cells and podocytes. Macula densa cells stained positively. Similar localization of the AT1 receptor was obtained using the three tissue fixation methods, although the intensity of vascular and glomerular staining was highest in Bouin-fixed tissues. The present study demonstrates that the AT1 receptor is more widely distributed along the nephron than previously described and includes renal vascular smooth muscle and proximal and distal epithelial sites.

Amino Acid Sequence↗
PubMed1996

Paracrine regulation of the renal microcirculation.

There has been an explosive growth of interest in the multiple interacting paracrine systems that influence renal microvascular function. This review first discusses the membrane activation mechanisms for renal vascular control. Evidence is provided that there are differential activating mechanisms regulating pre- and postglomerular arteriolar vascular smooth muscle cells. The next section deals with the critical role of the endothelium in the control of renal vascular function and covers the recent findings related to the role of nitric oxide and other endothelial-derived factors. This section is followed by an analysis of the roles of vasoactive paracrine systems that have their origin from adjoining tubular structures. The interplay of signals between the epithelial cells and the vascular network to provide feedback regulation of renal hemodynamics is developed. Because of their well-recognized contributions to the regulation of renal microvascular function, three major paracrine systems are discussed in separate sections. Recent findings related to the role of intrarenally formed angiotensin II and the prominence of the AT1 receptors are described. The possible contribution of purinergic compounds is then discussed. Recognition of the emerging role of extracellular ATP operating via P2 receptors as well as the more recognized functions of the P1 receptors provides fertile ground for further studies. In the next section, the family of vasoactive arachidonic acid metabolites is described. Possibilities for a myriad of interacting functions operating both directly on vascular smooth muscle cells and indirectly via influences on endothelial and epithelial cells are discussed. Particular attention is given to the more recent developments related to hemodynamic actions of the cytochrome P-450 metabolites. The final section discusses unique mechanisms that may be responsible for differential regulation of medullary blood flow by locally formed paracrine agents. Several sections provide perspectives on the complex interactions among the multiple mechanisms responsible for paracrine regulation of the renal microcirculation. This plurality of regulatory interactions highlights the need for experimental strategies that include integrative approaches that allow manifestation of indirect as well as direct influences of these paracrine systems on renal microvascular function.

Animals↗
PubMed1996

Renal cortical and medullary microvascular blood flow autoregulation in rat.

Previous studies have demonstrated the critical role of the afferent arteriole in autoregulation of nephron blood flow in response to changes in perfusion pressure. The present study focused on the responses of postglomerular vascular segments to alterations in renal arterial pressure. Afferent arterioles, efferent arterioles and outer medullary descending vasa recta of juxtamedullary nephrons were visualized using the in vitro blood-perfused juxtamedullary nephron technique. Simultaneous measurements of inside vessel diameter and centerline erythrocyte velocity were made in order to determine single vessel blood flow. Blood flow measured in afferent arterioles (N = 13) displayed efficient autoregulation of blood flow and afferent arterioles responded actively with decreases in arteriolar diameter during stepwise elevations of renal perfusion pressure from 100 to 150 mm Hg. Similarly, blood flow measured at efferent arterioles (N = 9) exhibited autoregulation during increases in renal perfusion pressure. However, efferent arteriolar diameters were not altered during increases in perfusion pressure. During superfusion with the calcium channel blocker, diltiazem (10 microM), which primarily dilates afferent arterioles, efferent arteriolar blood flow (N = 7) increased and responded to changes in perfusion pressure. Nevertheless, efferent arteriolar diameter remained unchanged and did not respond to increases in perfusion pressure. Outer medullary descending vasa recta (N = 7) diameter, centerline erythrocyte velocity and calculated blood flow were also not significantly altered following stepwise increases in pressure to 125 and 150 mm Hg. These data demonstrate effective autoregulation of postglomerular blood flow, measured at efferent arterioles and at outer medullary descending vasa recta, over a perfusion pressure range of 100 to 150 mm Hg. There was no dissociation of arteriolar and outer medullary descending vasa recta blood flow responses to increases in renal perfusion pressure indicative of efficient autoregulation in both cortical and medullary postglomerular circulations of the rat.

Animals↗
PubMed1995

Impact of cyclo-oxygenase blockade on juxtamedullary microvascular responses to angiotensin II in rat kidney.

1. Experiments were designed to evaluate the hypothesis that cyclo-oxygenase products modulate the influence of angiotensin II (AII) on the renal juxtamedullary microvasculature of enalaprilat-treated rats. 2. The in vitro blood-perfused juxtamedullary nephron technique was utilized to provide access to afferent arterioles, efferent arterioles and descending vasa recta located in the outer stripe of the outer medulla. 3. Baseline afferent arteriolar diameter was 20.8 +/- 1.9 microns in kidneys subjected to cyclo-oxygenase blockade (1 mumol/L piroxicam), a value significantly lower than that observed in untreated kidneys (26.1 +/- 1.0 microns). Baseline diameters of efferent arterioles and outer medullary descending vasa recta did not differ between untreated and piroxicam-treated groups. 4. Topical application of 1 nmol/L AII reduced blood flow through outer medullary descending vasa recta by 22 +/- 6% in untreated kidneys and by 24 +/- 7% in piroxicam-treated kidneys. 5. In untreated kidneys, AII (0.01-100 nmol/L) produced concentration-dependent afferent and efferent arteriolar constrictor responses of similar magnitudes. Neither afferent nor efferent arteriolar AII responsiveness was significantly altered in piroxicam-treated kidneys, although afferent responses exceeded efferent responses at AII concentrations > or = 10 nmol/L. 6. We conclude that endogenous cyclo-oxygenase products exert a vasodilator influence on juxtamedullary afferent arterioles under baseline conditions. Although cyclo-oxygenase inhibition had little effect on juxtamedullary microvascular responses to AII, the response to high AII concentrations may be modulated by cyclo-oxygenase products in a manner which delicately alters the relative influence of the peptide on pre- vs postglomerular resistances.

Angiotensin II↗
PubMed1994

Juxtamedullary microvascular responses to arginine vasopressin in rat kidney.

Experiments were performed to determine the site of arginine vasopressin (AVP)-induced vascular resistance adjustments that result in decreases in papillary blood flow. Simultaneous measurements of luminal diameter and centerline erythrocyte velocity allowed estimation of single-vessel blood flow in in vitro blood-perfused juxtamedullary nephrons. AVP (0.1-1,000 pM) caused concentration-dependent reductions in outer medullary descending vasa recta (OMDVR) blood flow (10 pM) without altering OMDVR diameter. Afferent arteriolar diameter was significantly decreased by 1 pM AVP, whereas arcuate artery diameter was decreased by 100 pM AVP. Increasing the concentration of AVP to 1,000 pM resulted in significant reductions of vessel diameter in interlobular arteries, distal afferent arterioles, and efferent arterioles. The effects of AVP to decrease afferent arteriolar diameter and blood flow were blocked in the presence of V1 receptor antagonist. These data indicate that afferent arterioles exhibit the greatest sensitivity to the vasoconstrictor effects of AVP, whereas OMDVR appear insensitive. We conclude that the change in OMDVR blood flow produced by AVP is not due to a direct effect of the peptide on this vascular segment but to its effect on upstream vessels.

Animals↗
PubMed1994

Autoregulation of afferent arteriolar blood flow in juxtamedullary nephrons.

Utilizing the in vitro blood-perfused juxtamedullary nephron preparation, we examined the effects of alterations in renal arterial pressure on afferent arteriolar blood flow. With video microscopy and cross-correlation techniques, arteriolar inside diameters and centerline erythrocyte velocity were measured to estimate single afferent arteriolar blood flow. In response to random changes in perfusion pressure, afferent arteriolar diameter (n = 8) varied inversely (-0.53 +/- 0.02%/mmHg), and erythrocyte velocity was directly related (1.4 +/- 0.1%/mmHg). Above 95 mmHg, the slope of the relationship between perfusion pressure and afferent arteriolar blood flow did not differ from zero (0.081 +/- 0.053%/mmHg), suggesting efficient autoregulation. When the tubuloglomerular feedback pathway was interrupted by the addition of furosemide (n = 9) or papillectomy (n = 7), there was attenuation of pressure-induced afferent arteriolar constriction, with impairment in blood flow autoregulation (0.60 +/- 0.05%/mmHg). Superfusion with diltiazem abolished autoregulatory responses in afferent arteriolar diameter and blood flow (1.5 +/- 0.2%/mmHg). These data demonstrate the autoregulation of blood flow of individual afferent arterioles in juxtamedullary nephrons and suggest that both tubuloglomerular feedback-dependent and -independent mechanisms are required for autoregulatory responses.

Animals↗
PubMed1991

Chronic vs. acute hemodynamic effects of atrial natriuretic factor in conscious rats.

The present study was designed to examine acute (2 h) and chronic (5 day) effects of pathophysiological elevations of plasma atrial natriuretic factor (ANF) in conscious normotensive rats. Acute infusion of ANF (100 ng.kg-1.min-1; n = 15) resulted in a decrease in mean arterial pressure (MAP) of 5 +/- 3 mmHg, which was associated with a 23 +/- 4% decrease in cardiac output (CO) and a 27 +/- 6% increase in total peripheral resistance (TPR). Hematocrit increased from 41.9 +/- 0.7 to 46.0 +/- 0.6%, which is suggestive of vascular volume contraction. Chronic infusion of ANF (n = 9) produced a significant fall in MAP from a control value of 114 +/- 2 to 100 +/- 3 and 99 +/- 2 mmHg on days 1 and 5, respectively. CO decreased significantly (27 +/- 2%) and TPR increased (21 +/- 5%) on day 1; neither variable was significantly different from control on day 5. Plasma immunoreactive ANF levels were significantly elevated during acute (791 +/- 76 pg/ml) and chronic (626 +/- 202 pg/ml) ANF infusion compared with control values of approximately 100 pg/ml. The results indicate that elevations in plasma ANF within the pathophysiological range can significantly alter systemic hemodynamics, initially mediated by a decrease in CO. Autoregulatory phenomena may counteract these hemodynamic effects, returning CO to control levels and reducing TPR when the elevations in plasma ANF are chronically sustained.

Animals↗
PubMed1990

Renal versus hindquarter hemodynamic responses to vasopressin in conscious rats.

Experiments were performed on conscious rats to (a) compare the responsiveness of the renal and hindquarter vascular beds to infusions of exogenous arginine vasopressin (AVP), and (b) determine whether either bed demonstrates V2-vasopressinergic vasodilation when the vasoconstrictor properties of AVP are blocked. Rats were chronically instrumented with pulsed Doppler flow probes on either the left renal artery or the distal abdominal aorta as well as with femoral arterial and venous catheters. One series of experiments examined the vascular responses of these two beds to exogenous AVP infused intravenously (i.v.) at 0.2, 2.0, or 5.0 ng/min. The lowest infusion rate was associated with no detectable changes in mean arterial blood pressure (MAP), heart rate (HR), renal or hindquarter blood flow (RBF or HQBF), or vascular resistance in these beds. In contrast, the higher infusion rates caused a marked increase in MAP, a decrease in HR, and a reduction in HQBF; RBF was unaffected, however. A second series of experiments tested for the presence of a V2-vasodilatory influence during infusion of AVP at 5 ng/min by selectively blocking V1-vasopressinergic receptors or both V1- and V2-receptor types. Little evidence for V2-mediated vasodilation was found in either vascular bed, however. We conclude that although the renal vasculature appears relatively insensitive to exogenous AVP, this insensitivity probably is not due to vasodilation mediated by activation of V2-receptors.

Animals↗
PubMed1990

Sympathectomy fails to reveal prominent vasodilation by atrial natriuretic factor.

Reflex activation of the sympathetic nervous system may conceal direct vasodilatory actions of atrial natriuretic factor and mediate atrial natriuretic factor-induced increases in total peripheral resistance. We determined whether peripheral sympathectomy would enhance the hypotensive actions of atrial natriuretic factor and convert the increase in total peripheral resistance to peripheral vasodilation. Sympathectomized rats studied included 1) conscious rats treated with 6-hydroxydopamine alone (partially sympathectomized) and 2) conscious anephric rats sympathectomized with adrenal demedullation and 6-hydroxydopamine (totally sympathectomized), with vascular tone returned to levels of sham-operated (control) rats with norepinephrine infusion. Sympathectomized rats and appropriate control rats received rat atrial natriuretic factor infusion (0.5 microgram/kg/min) or vehicle for 1 hour. Atrial natriuretic factor infusion lowered mean arterial pressure and increased hematocrit in control rats but not in partially sympathectomized rats. Changes in cardiac output and total peripheral resistance were not significantly different between control and partially sympathectomized rats. In totally sympathectomized rats, atrial natriuretic factor lowered mean arterial pressure more than in control rats; changes in cardiac output were nearly identical in both groups, but there were no changes in total peripheral resistance from control levels in the totally sympathectomized group. Changes in plasma volume and central venous pressure were similar in totally sympathectomized rats and control rats. These findings suggest that reflex sympathetic activity largely mediated atrial natriuretic factor-induced increases in total peripheral resistance but failed to reveal an atrial natriuretic factor-mediated sustained vasodilation in the absence of sympathetic reflexes. Furthermore, atrial natriuretic factor decreased cardiac output, central venous pressure, and plasma volume independent of the sympathetic nervous system.

Adrenal Medulla↗
PubMed1988

Potentiated vasoconstrictor response to vasopressin following meclofenamate in conscious rats.

Experiments were performed to test the hypothesis that release of vasodilator cyclooxygenase products may attenuate the systemic and renal vasoconstrictor responses to arginine vasopressin (AVP) in the conscious, chronically instrumented rat. Four groups of animals were studied under the following conditions: (i) AVP infused iv at 2 ng/min for 40 min followed by a 15-min postcontrol; (ii) pretreatment with meclofenamate (3 mg/kg iv) followed by AVP infusion; (iii) meclofenamate pretreatment followed by saline vehicle infusion; and (iv) saline vehicle infusion alone (time control). AVP increased mean arterial blood pressure (MABP) in both meclofenamate-treated (n = 12) and untreated (n = 12) animals; however, the pressor response was significantly greater in animals with cyclooxygenase inhibition. Both heart rate (HR) and cardiac output (CO) (n = 6) fell during AVP infusion, but there were no differences between the meclofenamate-treated and the untreated groups. However, the total peripheral resistance response to AVP was significantly greater in animals treated with meclofenamate than the untreated group. Renal blood flow (RBF) was not affected by AVP infusion alone, but RBF fell significantly in animals given AVP after cyclooxygenase inhibition. The renal vascular resistance response to AVP was also enhanced by cyclooxygenase inhibition. There were no changes in any of the hemodynamic variables in either of the control protocols (i.e., meclofenamate alone or vehicle). These data demonstrate a consistent effect of cyclooxygenase inhibition to augment the systemic and renal vasoconstrictor responses to AVP, and suggest that endogenous vasodilator prostaglandins attenuate the potent vasoconstrictor action of this peptide in vivo.

Animals↗
PubMedDate not supplied

Microvascular effects of atrial natriuretic peptide in rat cremaster.

Experiments utilized the open cremaster preparation to test the hypothesis that atrial natriuretic peptide (ANP)-induced volume changes result from microvascular resistance alterations. Atrial natriuretic peptide (25, 100, and 500 ng/kg/min, IV) or vehicle was infused into anesthetized rats. At the two highest ANP infusion rates, mean arterial pressure was significantly reduced from 104 +/- 3 (control) to 87 +/- 2 and 77 +/- 2 mmHg, respectively. Hematocrit was 41.0 +/- 0.8 and 45.6 +/- 0.9% (p < 0.05) at the end of vehicle and ANP infusions, respectively. Despite these effects of ANP, there were no significant arteriolar or venular diameter alterations. Thirty microM nitroprusside significantly dilated all vessel segments except large venules. These observations suggest that resistance alterations in the skeletal muscle microvasculature are not the cause of ANP-induced fluid movement.

Animals↗