Exaggerated renal vascular reactivity to angiotensin and thromboxane in young genetically hypertensive rats

1990 ◽  
Vol 259 (2) ◽  
pp. F372-F382 ◽  
Author(s):  
C. Chatziantoniou ◽  
F. H. Daniels ◽  
W. J. Arendshorst
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Renal Blood Flow ◽  
Receptor Agonist ◽  
Vascular Reactivity ◽  
Prostaglandin Synthesis ◽  
Genetic Hypertension ◽  
Inhibition Of Prostaglandin Synthesis ◽  
Renal Vascular

The objective of this study was to test the hypothesis that angiotensin II and thromboxane A2 (TxA2) contribute to the elevated renal vascular resistance observed during the development of genetic hypertension. In 6-wk-old anesthetized spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats, renal blood flow (electromagnetic flowmetry) and carotid arterial pressure were measured during bolus injections of different doses of angiotensin II and U46619 (stable receptor agonist of TxA2) into the renal artery before and during inhibition of prostaglandin synthesis by indomethacin. In all cases, arterial pressure remained unchanged at the pre-injection levels. Under control conditions, angiotensin II reduced renal blood flow in SHR almost twice as much as in WKY. This strain difference was abolished by inhibition of prostaglandin synthesis, suggesting that a deficiency in the action of endogenous vasodilator prostaglandins is responsible for the enhanced response to angiotensin II in SHR. Under control conditions, the TxA2-receptor agonist produced similar reductions of renal blood flow in SHR and WKY. However, after indomethacin, the agonist-induced vasoconstriction was twice as large in SHR as in WKY, suggesting that SHR kidneys have an increased vascular reactivity to TxA2, which is unmasked when indomethacin reduces elevated levels of endogenous TxA2. These findings indicate important strain differences between young SHR and WKY in the renal vascular response to angiotensin II and TxA2 that may contribute to the renal vasoconstriction observed during the development of genetic hypertension.

Cyclosporine augments renal but not systemic vascular reactivity

1990 ◽  
Vol 258 (1) ◽  
pp. F211-F217
Author(s):  
M. D. Garr ◽  
M. S. Paller
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Renal Blood Flow ◽  
Arginine Vasopressin ◽  
Vascular Reactivity ◽  
Pressor Response ◽  
Sprague Dawley ◽  
Renal Vasoconstriction ◽  
Vascular Responsiveness ◽  
Renal Vascular

Renal vasoconstriction and hypertension are major side effects of cyclosporine. We tested the acute effects of cyclosporine on renal and systemic vascular reactivity to norepinephrine, angiotensin II, and arginine vasopressin. Renal vascular reactivity was tested in anesthetized Sprague-Dawley rats with denervated kidneys. Renal blood flow was measured with an electromagnetic flow probe in response to graded intra-arterial infusions of vasoconstrictors before and after intravenous administration of cyclosporine. Cyclosporine augmented the decrease in renal blood flow and the increase in renal vascular resistance produced by intrarenal norepinephrine, angiotensin II, and arginine vasopressin. In these studies, systemic blood pressure did not change and cyclosporine caused no direct change in basal renal blood flow. In contrast, in conscious animals, cyclosporine did not increase the pressor response to intravenous norepinephrine or to angiotensin II. Rather, cyclosporine caused enhanced baroreflex slowing of heart rate and a decrease in the pressor response to both norepinephrine and angiotensin II. Even when the baroreceptor reflex was blocked by pentolinium, the pressor response to norepinephrine in cyclosporine-treated animals was diminished compared with vehicle-treated animals. Therefore, although cyclosporine augmented renal vasoconstriction in response to norepinephrine, angiotensin II, and arginine vasopressin, it did not acutely increase the systemic vascular response to these agents. Enhanced renal vascular responsiveness is an additional mechanism for cyclosporine-mediated renal vasoconstriction. Lack of enhanced peripheral vascular responsiveness suggests that hypertension is not likely to be due to direct effects on the systemic vasculature and is more likely to be a consequence of renal functional impairment.

scholarly journals Heme oxygenase activity as a determinant of the renal hemodynamic response to low-dose ANG II

2010 ◽  
Vol 299 (5) ◽  
pp. R1183-R1191 ◽  
Author(s):  
Karl A. Nath ◽  
Melissa C. Hernandez ◽  
Anthony J. Croatt ◽  
Zvonimir S. Katusic ◽  
Luis A. Juncos
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Blood Flow ◽  
Arterial Pressure ◽  
Renal Blood Flow ◽  
Heme Oxygenase ◽  
Vascular Reactivity ◽  
Ang Ii ◽  
Related Gene ◽  
Renal Vascular

ANG II causes renal injury through hemodynamic and other effects, and pressor doses of ANG II induce heme oxygenase-1 (HO-1) as a protective response. The present studies examined the hemodynamic effects of more clinically relevant, lower doses of ANG II and the role of HO activity in influencing these effects. Under euvolemic conditions, ANG II increased arterial pressure and renal vascular resistance. ANG II did not induce oxidative stress, inflammation/injury-related gene expression, or proteinuria and did not alter extrarenal vascular reactivity. At these doses, ANG II failed to increase HO-1 or HO-2 mRNA expression or HO activity. Inhibiting HO activity in ANG II-treated rats by tin mesoporphyrin further increased renal vascular resistances, decreased renal blood flow, and blunted the rise in arterial pressure without inducing oxidative stress or altering expression of selected vasoactive/injury/inflammation-related genes; tin mesoporphyrin did not alter vasorelaxation of mesenteric resistor vessels. We conclude that in this model renal vasoconstriction occurs without the recognized adverse effects of ANG II on glomerular filtration rate, renal blood flow, oxidative stress, vascular reactivity, proteinuria, and injury-related gene expression; renal HO activity is essential in preserving perfusion of the ANG II-exposed kidney. These findings represent an uncommon example wherein function of a stressed organ (by ANG II), but not that of the unstressed organ, requires intact renal HO activity, even when the imposed stress neither induces HO-1 nor HO activity. These findings may be germane to conditions attended by heightened ANG II levels, ineffective renal perfusion, and susceptibility to acute kidney injury.

Effects of Saralasin Infusion on Bilateral Renal Function in Two-Kidney, One-Clip Goldblatt Hypertensive Rats

1982 ◽  
Vol 62 (6) ◽  
pp. 573-579 ◽  
Author(s):  
Wann-Chu Huang ◽  
D. W. Ploth ◽  
L. G. Navar
Keyword(s):  
Blood Flow ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Renal Blood Flow ◽  
Filtration Rate ◽  
Hypertensive Rats ◽  
Excretory Function ◽  
Renal Vascular

1. Previous studies have shown that administration of converting enzyme inhibitor (CEI, SQ 20 881) to two-kidney, one-clip Goldblatt hypertensive (GH) rats clipped for 3–4 weeks resulted in marked increases in glomerular filtration rate (GFR), water and sodium excretion by the non-clipped kidneys. The clipped kidneys exhibited reduced function that was due, in part, to the reductions in arterial pressure. To evaluate further the hypothesis that the renal responses to CEI were due primarily to the inhibition of angiotensin II rather than other factors, we infused the angiotensin II competitive blocker, saralasin, into GH rats under sodium pentobarbital anaesthesia and examined renal haemodynamics and excretory function of each kidney before and during saralasin infusion and after cessation of saralasin infusion. 2. Saralasin reduced mean arterial blood pressure from 164 ± 4 to 124 ± 4 mmHg. Despite the profound fall of arterial pressure, significant increases in renal blood flow from 5.82 ± 0.22 to 9.15 ± 0.76 ml/min and glomerular filtration rate from 1.46 ± 0.10 to 2.18 ± 0.14 ml/min were observed in the non-clipped kidneys. Renal vascular resistance decreased from 2.34 (± 0.14) × 105 to 1.17 (± 0.19) × 105 kPa l−1 s [2.34 (± 0.14) × 106 to 1.17 (± 0.19) × 106 dyn s cm−5]. Also, concomitant diuresis and kaliuresis and a delayed natriuresis occurred. Correspondence: Dr L. G. Navar, University of Alabama in Birmingham Medical Center, University Station, 727 CDLD Bldg, Birmingham, Alabama 35294, U.S.A. 3. The clipped kidneys exhibited reductions in renal blood flow, GFR and excretory function during saralasin infusion. 4. Normal rats receiving the identical dose of saralasin responded with a slight but significant decrease in arterial pressure. The increases in renal blood flow and GFR were less than those observed in the non-clipped kidneys of hypertensive rats. 5. These data provide further support to the hypothesis that an angiotensin II-mediated elevation in renal vascular resistance and impairment of renal function exist in the non-clipped kidneys of GH rats.

Renal hemodynamics and vascular reactivity in canine DOCA-salt hypertension

1988 ◽  
Vol 255 (4) ◽  
pp. R563-R568
Author(s):  
J. L. Goering ◽  
P. C. Raich ◽  
B. G. Zimmerman
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Vascular Tone ◽  
Vascular Reactivity ◽  
Control Period ◽  
Indwelling Catheter ◽  
Alpha Adrenoceptor ◽  
Arterial Blood ◽  
Salt Hypertension ◽  
Renal Vascular

Because of the potential role that the kidney may play in deoxycorticosterone acetate (DOCA)-salt hypertension, changes in renal blood flow, renal vascular reactivity, and renal adrenergic vascular tone were followed in the conscious instrumented dog. DOCA-salt was administered daily after obtaining control measurements. Systemic mean arterial blood pressure (MAP) was monitored with an indwelling catheter, renal blood flow (RBF) was measured electromagnetically using an implanted blood flow probe, and drugs were administered intrarenal arterially through an indwelling renal artery catheter. During the first week of DOCA-salt administration MAP increased from 106 +/- 3 to 118 +/- 2 mmHg and at week 2 to 123 +/- 2 mmHg (P less than 0.01). RBF increased from 275 +/- 32 to 336 +/- 34 during week 1 (P less than 0.05) and to 324 +/- 29 ml/min during week 2. The log ED50 of norepinephrine administered intra-arterially decreased from 1.66 +/- 0.114 to 1.48 +/- 0.091 and 1.41 +/- 0.067 ng/ml (P less than 0.05), and of angiotensin II from 2.58 +/- 0.072 to 2.31 +/- 0.09 (P less than 0.05) and 2.38 +/- 0.05 pg/ml, during weeks 1 and 2, respectively. There was, however, no increase in adrenergic vascular tone as determined by the change in RBF obtained with the intra-arterial infusion of alpha-adrenoceptor antagonists. These experiments indicate that RBF is not compromised in canine DOCA-salt hypertension, and renal adrenergic tone is no greater in the hypertensive than in the normotensive control period.

Enhanced renal vasoconstriction induced by vasopressin in SHR is mediated by V1 receptors

1996 ◽  
Vol 271 (2) ◽  
pp. F304-F313 ◽  
Author(s):  
J. J. Feng ◽  
W. J. Arendshorst
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Arginine Vasopressin ◽  
Receptor Agonist ◽  
Vascular Reactivity ◽  
Spontaneously Hypertensive Rat ◽  
Rat Kidney ◽  
Strain Difference ◽  
Renal Vasoconstriction ◽  
V2 Receptor

The development of hypertension in the spontaneously hypertensive rat (SHR) is associated with renal dysfunction; the observed renal vasoconstriction may reflect an imbalance of constrictor and dilator systems. The present studies evaluated renal vascular reactivity to arginine vasopressin (AVP) and mediation by V1 and/or V2 receptors. Renal blood flow (electromagnetic flowmetry) was measured in water-loaded, 8-wk-old SHR, Wistar-Kyoto rats (WKY), and Munich-Wistar rats. Injection of AVP (2 and 5 ng) into the renal artery caused dose-dependent renal vasoconstriction. The maximum blood flow response was approximately twofold larger in SHR than both normotensive strains. The strain difference was largely unaffected by indomethacin administration, although the reduction in blood flow produced by 5 ng AVP was 4-6% larger in both SHR and WKY during cyclooxygenase inhibition. The V1 receptor antagonist, [D-(CH2)5,Tyr(Me)2,Tyr(NH2)9]Arg8-vasopressin, blocked up to 90% of the renal vasoconstriction elicited by AVP. Intrarenal injection of the V1-receptor agonist [Phe2,Ile3,Org8]vasopressin produced renal hemodynamic effects similar to AVP; this agonist reduced renal blood flow, with twofold larger responses in SHR (-40 vs. -18% for 10 ng). In contrast, similar doses of the V2-receptor agonist 1-desamino-8-D-arginine vasopressin had no effect. These results indicate that AVP-induced vasoconstriction is mediated predominantly by the V1 receptor in the rat kidney. The enhanced vascular reactivity in 8-wk-old SHR may reflect an increased V1 receptor density and/or affinity or postreceptor signaling pathways, largely independent of buffering by the vascular V2 receptor or vasodilator prostaglandin activity. The strain difference in the vascular response to AVP may contribute to the renal vasoconstriction observed during the development of genetic hypertension.

Renal vasodilatation after inhibition of renin or converting enzyme in marmoset

1986 ◽  
Vol 251 (5) ◽  
pp. H897-H902
Author(s):  
D. Neisius ◽  
J. M. Wood ◽  
K. G. Hofbauer
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Angiotensin Ii ◽  
Renal Blood Flow ◽  
Vascular Resistance ◽  
Enzyme Inhibitor ◽  
Renal Vascular Resistance ◽  
Converting Enzyme ◽  
Renin Inhibition ◽  
Renal Vascular

The relative importance of angiotensin II for the renal vasodilatory response after converting-enzyme inhibition was evaluated by a comparison of the effects of converting-enzyme and renin inhibition on renal vascular resistance. Renal, mesenteric, and hindquarter blood flows were measured with chronically implanted ultrasonic-pulsed Doppler flow probes in conscious, mildly volume-depleted marmosets after administration of a converting-enzyme inhibitor (enalaprilat, 2 mg/kg iv), a synthetic renin inhibitor (CGP 29,287, 1 mg/kg iv), or a renin-inhibitory monoclonal antibody (R-3-36-16, 0.1 mg/kg iv). Enalaprilat reduced blood pressure (-16 +/- 4 mmHg, n = 6) and induced a selective increase in renal blood flow (27 +/- 8%, n = 6). CGP 29,287 and R-3-36-16 induced comparable reductions in blood pressure (-16 +/- 4 mmHg, n = 6 and -20 +/- 4 mmHg, n = 5, respectively) and selective increases in renal blood flow (36 +/- 12%, n = 6 and 34 +/- 16%, n = 4, respectively). The decrease in renal vascular resistance was of similar magnitude for all of the inhibitors (enalaprilat -28 +/- 3%, CGP 29,287 -32 +/- 6%; and R-3-36-16 -33 +/- 7%). These results indicate that the renal vasodilatation induced after converting-enzyme or renin inhibition is mainly due to decreased formation of angiotensin II.

Effect of prostaglandin synthetase inhibitors on renal blood flow in the rat

1976 ◽  
Vol 231 (5) ◽  
pp. 1541-1545 ◽  
Author(s):  
WF Finn ◽  
WJ Arendshorst
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Renal Blood Flow ◽  
Perfusion Pressure ◽  
Small Diameter ◽  
Base Line ◽  
Sodium Pentobarbital ◽  
Prostaglandin Synthetase ◽  
Flow Transducer ◽  
Renal Vascular

Using a small-diameter electromagnetic flow transducer, the effect on the autoregulation of renal blood flow (RBF) of two structurally different prostaglandin synthetase inhibitors, indomethacin, 4 mg/kg BW, and meclofenamate, 5 mg/kg BW, was studied in nondiuretic rats anesthetized with either the oxybarbiturate, sodium pentobarbital, or the thiobarbiturate, Inactin. Regardless of the anesthetic agent, RBF remained relatively constant above a perfusion pressure of 105 mmHg. Treatment with either indomethacin or meclofenamate had no measurable effect on the autoregulatory response. Each agent, however, resulted in an increase in the renal vascular response to exogenous angiotensin II, an effect consistent with prostaglandin synthetase inhibition. Base-line RBF was significantly reduced by indomethacin or meclofenamate only in those animals that had previously received angiotensin. These results support the hypothesis that, in th rat, autoregulation of RBF occurs independently of prostaglandin activity, but that a relationship does exist between the renal vascular actions of angiotensin II and prostaglandins.

scholarly journals Losartan does not decrease renal oxygenation and norepinephrine effects in rats after resuscitated hemorrhage

2018 ◽  
Vol 315 (2) ◽  
pp. F241-F246
Author(s):  
Sofia Jönsson ◽  
Jacqueline M. Melville ◽  
Mediha Becirovic-Agic ◽  
Michael Hultström
Keyword(s):  
Blood Flow ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Renal Blood Flow ◽  
Oxygen Tension ◽  
Vascular Resistance ◽  
Renal Vascular Resistance ◽  
Renal Oxygen Consumption ◽  
Significant Difference ◽  
Renal Vascular

Renin-angiotensin-system blockers are thought to increase the risk of acute kidney injury after surgery and hemorrhage. We found that losartan does not cause renal cortical hypoxia after hemorrhage in rats because of decreased renal vascular resistance, but we did not evaluate resuscitation. We aimed to study losartan’s effect on renal cortical and medullary oxygenation, as well as norepinephrine’s vasopressor effect in a model of resuscitated hemorrhage. After 7 days of losartan (60 mg·kg−1·day−1) or control treatment, male Wistar rats were hemorrhaged 20% of their blood volume and resuscitated with Ringerʼs acetate. Mean arterial pressure, renal blood flow, and kidney tissue oxygenation were measured at baseline and after resuscitation. Finally, the effect of norepinephrine on mean arterial pressure and renal blood flow was investigated. As expected, losartan lowered mean arterial pressure but not renal blood flow. Losartan did not affect renal oxygen consumption and oxygen tension. Mean arterial pressure and renal blood flow were lower after resuscitated hemorrhage. A smaller increase of renal vascular resistance in the losartan group translated to a smaller decrease in cortical oxygen tension, but no significant difference was seen in medullary oxygen tension, either between groups or after hemorrhage. The effect of norepinephrine on mean arterial pressure and renal blood flow was similar in control- and losartan-treated rats. Losartan does not decrease renal oxygenation after resuscitated hemorrhage because of a smaller increase in renal vascular resistance. Further, losartan does not decrease the efficiency of norepinephrine as a vasopressor, indicating that blood pressure may be managed effectively during losartan treatment.

Alteration of canine renal vascular response to hemorrhage by inhibitors of prostaglandin synthesis

1976 ◽  
Vol 230 (4) ◽  
pp. 940-945 ◽  
Author(s):  
JL Data ◽  
LC Chang ◽  
AS Nies
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Control Period ◽  
Prostaglandin Synthesis ◽  
Hemorrhagic Hypotension ◽  
Renal Cortical Blood Flow ◽  
Renal Vascular ◽  
Inner Cortex ◽  
Equal Thickness ◽  
Total Renal Blood Flow

The involvement of prostaglandins in the redistribution of renal cortical blood flow to inner cortical nephrons during hemorrhagic hypotension was studied in the pentobarbital-anesthetized dog. Total renal blood flow and distribution of renal cortical flow were determined with the radioactive microsphere technique by dividing the cortex into four zones of equal thickness, zone 1 being outermost and zone 4 being juxtamedullary. Two inhibitors of prostaglandin synthesis were used: indomethacin 8 mg/kg and aspirin 100 mg/kg. The inhibitor or the vehicle was given intravenously prior to a control period which was followed by a hemorrhage sufficient to decrease arterial pressure by about one-third. The distribution of cortical flow was determined before hemorrhage, during hemorrhagic hypotension, and after transfusion. In the vehicle-treated dogs, total renal blood flow was well maintained, but flow redistributed to favor the inner cortical nephrons. This vasodilation in the inner cortex was blocked by both inhibitors of prostaglandin synthesis resulting in a decrease in total renal blood flow and relative ischemia of the juxtamedullary nephrons. Salicylate levels required to accomplish blockage of inner cortical vasodilaton were less than 7 mg/100 ml. These studies indicate that prostaglandins are responsible for the decreased vascular resistance of the inner cortical nephrons which results in the redistribution of blood flow during hemorrhage, and when prostaglandin synthesis is blocked, the kidney vasculature constricts during hemorrhage.

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