Altered pressor responses to NE and ANG II during cyclosporin A administration to conscious rats

1990 ◽  
Vol 258 (3) ◽  
pp. H854-H860 ◽  
Author(s):  
S. C. Textor ◽  
L. Smith-Powell ◽  
T. Telles
Keyword(s):  
Angiotensin Ii ◽  
Cyclosporin A ◽  
Dose Response ◽  
Peak Effect ◽  
Relative Resistance ◽  
Pressor Responses ◽  
Induced Hypertension ◽  
Vascular Responsiveness ◽  
Renal Vascular ◽  
Conscious Animals

Vasoconstriction and hypertension have been prominent during cyclosporin A (CSA) administration. To evaluate whether CSA modulates vascular responsiveness to pressor stimuli in the intact organism, CSA was administered via osmotic pump (10 and 20 mg.kg-1.day-1 ip vs. olive oil vehicle) for 2 wk. After 8 days, arterial pressure and dose-response relationships to norepinephrine, angiotensin II, and bradykinin were measured in conscious animals. Despite similar initial pressures, dose-response relationships were markedly attenuated to both norepinephrine and angiotensin II. Maximal responses were not affected, indicating a rightward shift without loss of peak effect. Vasodilation with bradykinin was not diminished. These changes were not evident after an acute CSA infusion at the same dose (10 mg.kg-1.day-1 over 2 h). Treatment with verapamil (0.505 mg/kg over 2 days) lowered basal arterial pressures but did not change the effects of CSA on pressor sensitivity. Despite attenuated pressor responses, renal vascular resistance was elevated and glomerular filtration diminished during CSA administration. These observations indicate that cyclosporin modifies vascular responsiveness to pressor stimuli in the rat and may explain the relative resistance of this species to cyclosporin-induced hypertension.

Metabolic clearance of angiotensin II in pregnant and nonpregnant sheep

1985 ◽  
Vol 249 (1) ◽  
pp. E49-E55 ◽  
Author(s):  
R. P. Naden ◽  
S. Coultrup ◽  
B. S. Arant ◽  
C. R. Rosenfeld
Keyword(s):  
Angiotensin Ii ◽  
Pressor Response ◽  
Plasma Concentrations ◽  
Metabolic Clearance ◽  
Ang Ii ◽  
Pressor Responses ◽  
Pregnant Sheep ◽  
Vascular Responsiveness ◽  
Arterial Plasma ◽  
In Pregnancy

Reduced vascular responsiveness to infused angiotensin II (ANG II) has been observed during pregnancy. It has been proposed that infusions produce lower circulating concentrations of ANG II in pregnancy, due to an increase in the metabolic clearance rate of ANG II (MCRangii). We have evaluated the MCRangii and the arterial plasma concentrations of ANG II during constant infusions of 1.15 micrograms ANG II/min into chronically instrumented pregnant (n = 6) and nonpregnant (n = 9) sheep. Although the pressor responses were significantly less in the pregnant than in the nonpregnant sheep (17.5 +/- 0.5 vs. 34.9 +/- 3.2 mmHg, P less than 0.001), the values for MCRangii were not different: 56.2 +/- 6.3 ml X min-1 X kg-1 in nonpregnant and 55.9 +/- 4.3 ml X min-1 X kg-1 in pregnant sheep. The steady-state plasma ANG II concentrations during the infusions were slightly less in pregnant than in nonpregnant sheep (388 +/- 36 vs. 454 +/- 36 pg/ml); however, this difference would be responsible for only a 2-mmHg reduction in the pressor response. We conclude that the reduced pressor response to infused ANG II in pregnancy is not due to an increase in MCRangii nor to lower plasma ANG II concentrations.

scholarly journals Enhanced Renal Vascular Responsiveness to Angiotensin II and Norepinephrine: A Unique Feature of Female Rats with Congestive Heart Failure

2019 ◽  
Vol 44 (5) ◽  
pp. 1128-1141 ◽  
Author(s):  
Vojtěch Krátký ◽  
Soňa Kikerlová ◽  
Zuzana Husková ◽  
Janusz Sadowski ◽  
František Kolář ◽  
...  
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Renal Dysfunction ◽  
Unique Feature ◽  
Female Rats ◽  
Male Rats ◽  
Published Data ◽  
Ang Ii ◽  
Vascular Responsiveness ◽  
Renal Vascular

Background/Aims: We found recently that the aortocaval fistula (ACF)-induced heart failure (HF) results in higher mortality in female than in male rats. Possibly, the development of renal dysfunction in the females, unlike in males, is associated with altered renal vascular responsiveness to angiotensin II (ANG II). Methods: Five or 20 weeks after ACF creation (compensated and decompensated HF, respectively), we assessed renal blood flow (RBF) responses to intrarenal administration of ANG II, norepinephrine (NE), and acetylcholine (Ach) in female ACF and sham-operated rats. Results: In ACF females, ANG II decreased RBF more than in healthy animals, unlike with earlier published data in male ACF rats that responded similarly. Also, NE decreased RBF more in female ACF rats, whereas Ach increased RBF to the same extent in female ACF and sham-operated rats. RBF responses to intravenous administration of NE and Ach were almost identical in female and male ACF rats. Conclusion: Female ACF rats studied at the onset of HF decompensation reveal, in contrast to male rats, enhanced renal vascular responsiveness to both NE and ANG II. When associated with the demonstrated increased intrarenal ANG II and NE concentrations, such hyperresponsiveness might promote the development of renal dysfunction and accelerate HF decompensation.

Effects of SQ 20881 and captopril on mesenteric, renal, and iliac vasculatures

1983 ◽  
Vol 244 (3) ◽  
pp. H313-H319 ◽  
Author(s):  
M. J. Fiksen-Olsen ◽  
S. L. Britton ◽  
P. C. Houck ◽  
J. C. Romero
Keyword(s):  
Angiotensin Ii ◽  
Potent Inhibitor ◽  
Angiotensin I ◽  
Vascular Effects ◽  
Renal Vasculature ◽  
Kininase Ii ◽  
Equimolar Dose ◽  
Vascular Responsiveness ◽  
Vascular Beds ◽  
Renal Vascular

The ability of two kininase II inhibitors, SQ 20881 and captopril, to inhibit conversion of angiotensin I to angiotensin II and to potentiate the vascular responsiveness to exogenous bradykinin were compared in the mesenteric, renal, and external iliac vasculatures of the dog. Basal rate of angiotensin I-to-angiotensin II conversion was found to be lower in the renal vasculature, average conversion being 4.7%, than in the mesenteric and iliac vasculatures, in which the average conversion was 30.7 and 26.3%, respectively. Inhibition of angiotensin I conversion by both kininase II inhibitors was independent of the basal angiotensin I conversion rate; however, SQ 20881 was a more potent inhibitor of angiotensin I conversion than captopril in all vascular beds tested. In the presence of equal molar doses of SQ 20881 and captopril, only 20-30% of the control bradykinin doses was needed to produce the same vascular effects in the mesenteric and iliac vasculatures. In the kidney, 70% of the control bradykinin doses was needed to produce the same vascular effects in the presence of SQ 20881; in contrast to SQ 20881, neither an equimolar nor 20 times an equimolar dose of captopril produced any change in the renal vascular responsiveness to bradykinin. In conclusion, 1) SQ 20881 is a more potent inhibitor of angiotensin conversion than captopril, and 2) captopril, unlike SQ 20881, does not alter renal vascular responsiveness to bradykinin.

Evidence for renal vascular remodeling in angiotensin II-induced hypertension

2003 ◽  
Vol 21 (7) ◽  
pp. 1401-1406 ◽  
Author(s):  
Amanda J Edgley ◽  
Michelle M Kett ◽  
Warwick P Anderson
Keyword(s):  
Angiotensin Ii ◽  
Vascular Remodeling ◽  
Induced Hypertension ◽  
Renal Vascular

scholarly journals Role of the Na+/H+ exchanger 3 in angiotensin II-induced hypertension

2015 ◽  
Vol 47 (10) ◽  
pp. 479-487 ◽  
Author(s):  
Xiao C. Li ◽  
Gary E. Shull ◽  
Elisa Miguel-Qin ◽  
Jia L. Zhuo
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Glycogen Synthase ◽  
Proximal Tubules ◽  
Dependent Manner ◽  
Ang Ii ◽  
Lower Systolic Blood Pressure ◽  
Salt Wasting ◽  
Pressor Responses ◽  
Induced Hypertension

The renal mechanisms responsible for angiotensin II (ANG II)-induced hypertension remain incompletely understood. The present study tested the hypothesis that the Na+/H+ exchanger 3 (NHE3) is required for ANG II-induced hypertension in mice. Five groups of wild-type ( Nhe3 +/+) and Nhe3 −/− mice were treated with vehicle or high pressor doses of ANG II (1.5 mg/kg/day ip, via minipump for 2 wk, or 10 pmol/min iv for 30 min). Under basal conditions, Nhe3 −/− mice had significantly lower systolic blood pressure (SBP) and mean intra-arterial pressure (MAP) ( P < 0.01), 24 h urine ( P < 0.05), urinary Na+ ( P < 0.01) and urinary K+ excretion ( P < 0.01). In response to ANG II, SBP and MAP markedly increased in Nhe3 +/+ mice in a time-dependent manner, as expected ( P < 0.01). However, these acute and chronic pressor responses to ANG II were significantly attenuated in Nhe3 −/− mice ( P < 0.01). Losartan blocked ANG II-induced hypertension in Nhe3 +/+ mice but induced marked mortality in Nhe3 −/− mice. The attenuated pressor responses to ANG II in Nhe3 −/− mice were associated with marked compensatory humoral and renal responses to genetic loss of intestinal and renal NHE3. These include elevated basal plasma ANG II and aldosterone and kidney ANG II levels, salt wasting from the intestines, increased renal AQP1, Na+/HCO3−, and Na+/K+-ATPase expression, and increased PKCα, mitogen-activated protein kinases ERK1/2, and glycogen synthase kinase 3αβ signaling proteins in the proximal tubules ( P < 0.01). We concluded that NHE3 in proximal tubules of the kidney, along with NHE3 in intestines, is required for maintaining basal blood pressure as well as the full development of ANG II-induced hypertension.

scholarly journals Effects of Renal Denervation on the Enhanced Renal Vascular Responsiveness to Angiotensin II in High-Output Heart Failure: Angiotensin II Receptor Binding Assessment and Functional Studies in Ren-2 Transgenic Hypertensive Rats

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1803
Author(s):  
Zuzana Honetschlägerová ◽  
Lucie Hejnová ◽  
Jiří Novotný ◽  
Aleš Marek ◽  
Luděk Červenka
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Receptor Binding ◽  
Renal Denervation ◽  
Kidney Cortex ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Vascular Responsiveness ◽  
Renal Vascular ◽  
High Output

Detailed mechanism(s) of the beneficial effects of renal denervation (RDN) on the course of heart failure (HF) remain unclear. The study aimed to evaluate renal vascular responsiveness to angiotensin II (ANG II) and to characterize ANG II type 1 (AT1) and type 2 (AT2) receptors in the kidney of Ren-2 transgenic rats (TGR), a model of ANG II-dependent hypertension. HF was induced by volume overload using aorto-caval fistula (ACF). The studies were performed two weeks after RDN (three weeks after the creation of ACF), i.e., when non-denervated ACF TGR enter the decompensation phase of HF whereas those after RDN are still in the compensation phase. We found that ACF TGR showed lower renal blood flow (RBF) and its exaggerated response to intrarenal ANG II (8 ng); RDN further augmented this responsiveness. We found that all ANG II receptors in the kidney cortex were of the AT1 subtype. ANG II receptor binding characteristics in the renal cortex did not significantly differ between experimental groups, hence AT1 alterations are not responsible for renal vascular hyperresponsiveness to ANG II in ACF TGR, denervated or not. In conclusion, maintained renal AT1 receptor binding combined with elevated ANG II levels and renal vascular hyperresponsiveness to ANG II in ACF TGR influence renal hemodynamics and tubular reabsorption and lead to renal dysfunction in the high-output HF model. Since RDN did not attenuate the RBF decrease and enhanced renal vascular responsiveness to ANG II, the beneficial actions of RDN on HF-related mortality are probably not dominantly mediated by renal mechanism(s).

Disappearance of Angiotensin II and Noradrenaline from the Renal and Femoral Circulations of the Dog

1980 ◽  
Vol 58 (1) ◽  
pp. 29-35 ◽  
Author(s):  
M. J. S. Miller ◽  
G. C. Scroop
Keyword(s):  
Angiotensin Ii ◽  
Renal Artery ◽  
Femoral Artery ◽  
Pressor Response ◽  
Intravenous Route ◽  
Vascular Bed ◽  
Pressor Responses ◽  
Vascular Beds ◽  
Degree Of Extraction ◽  
Renal Vascular

1. The relative ability of the renal and femoral vascular beds to remove infused angiotensin II and noradrenaline was examined in anaesthetized greyhounds. 2. The degree of extraction of infused drug by each vascular bed was expressed as a percentage, calculated by comparing the pressor response to intra-arterial infusion with that obtained when the same dose was administered by the intravenous route. 3. When compared with the same dose given intravenously, the pressor responses after renal artery administration of angiotensin II were reduced by a mean of 77·8 ± 4·1% (mean ± sem, n = 12), whereas those after femoral artery infusions at the same dose were reduced by a mean of only 27·2 ± 4·9%(n = 12). 4. The pattern of extraction seen with noradrenaline infusions administered in a similar manner was the reverse of that with angiotensin II. There was a 28·9 ± 6·8% (n = 7) reduction in pressor responses to renal artery infusions; in contrast, femoral artery infusions of the same dose exhibited a 99·0 ± 1·0% (n = 7) reduction in the pressor responses. 5. Local arterial administration of the angiotensin II competitive antagonist, [Sar1,Ile8]angiotensin II, potentiated the systemic pressor responses to renal artery infusions of angiotensin II, but not those to femoral artery infusions. 6. It is suggested that the marked ability of the renal vascular bed to remove circulating angiotensin II may, in part, involve receptor-binding, although this seems not to be the case in the femoral vascular bed.

EFFECTS OF LONG-TERM EXTRARENAL ANGIOTENSIN II INFUSION ON RENAL VASCULAR RESPONSIVENESS TO VASOACTIVE AGENTS

1998 ◽  
Vol 25 (7-8) ◽  
pp. 633-636
Author(s):  
Sharyn M. Fitzgerald ◽  
Kathleen M. Stevenson ◽  
Roger G. Evans ◽  
Warwick P. Anderson
Keyword(s):  
Angiotensin Ii ◽  
Vasoactive Agents ◽  
Vascular Responsiveness ◽  
Renal Vascular

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.

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