Absence of Adrenergic Mediation of Agonist Response to [Sar1,Ala8]Angiotensin II in Conscious Normotensive and Hypertensive Dogs

1979 ◽  
Vol 57 (1) ◽  
pp. 71-81 ◽  
Author(s):  
B. G. Zimmerman
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Vascular Resistance ◽  
Intravenous Infusion ◽  
Direct Action ◽  
Renal Vascular Resistance ◽  
Angiotensin Receptors ◽  
Conscious Dog ◽  
Renal Vascular

1. In the conscious normotensive and two-kidney Goldblatt hypertensive dog a transient agonist response to the intravenous infusion of saralasin (1 μg min−1 kg−1) was manifested by a small increase in blood pressure (6–12 mmHg) and 28–30% increase in renal vascular resistance. 2. These increases in blood pressure and renal vascular resistance were unaffected by administration of either phentolamine or guanethidine. 3. The agonist response in the conscious dog is most likely accounted for by a direct action of saralasin on vascular angiotensin receptors.

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.

scholarly journals Angiotensin II blockade causes acute renal failure in eNOS-deficient mice

2001 ◽  
Vol 2 (1_suppl) ◽  
pp. S199-S203 ◽  
Author(s):  
Jürgen Schnermann ◽  
Yuning G Huang ◽  
Josie P Briggs
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Glomerular Filtration ◽  
Vascular Resistance ◽  
Knockout Mice ◽  
Renal Vascular Resistance ◽  
Wild Type ◽  
Arteriolar Tone ◽  
Renal Vascular ◽  
Deficient Mice

Compared with wild-type mice, adult endothelial nitric oxide synthase (eNOS) knockout mice (eight months of age) have increased blood pressure (BP) (126±9 mmHg vs. 100±4 mmHg), and an increased renal vascular resistance (155±16 vs. 65±4 mmHg.min/ml). Renal vascular resistance responses to i.v. administration of noradrenaline were markedly enhanced in eNOS knockout mice. Glomerular filtration rate (GFR) of anaesthetised eNOS -/- mice was 324±57 µl/min gKW, significantly lower than the GFR of 761±126 µl/min.gKW in wild-type mice. AT1-receptor blockade with i.v. candesartan (1—1.5 mg/kg) reduced arterial blood pressure and renal vascular resistance, and increased renal blood flow (RBF) to about the same extent in wild-type and eNOS -/- mice. Candesartan did not alter GFR in wild-type mice (761±126 vs. 720±95 µl/min.gKW), but caused a marked decrease in GFR in eNOS -/- mice (324.5±75.2 vs. 77±18 µl/min.gKW). A similar reduction in GFR of eNOS deficient mice was also caused by angiotensin-converting enzyme (ACE) inhibition. Afferent arteriolar granularity, a measure of renal renin expression, was found to be reduced in eNOS -/- compared with wild-type mice. In chronically eNOS-deficient mice, angiotensin II (Ang II) is critical for maintaining glomerular filtration pressure and GFR, presumably through its effect on efferent arteriolar tone.

Limb tourniquet and intramuscular clostridial toxin effects on renal function

1962 ◽  
Vol 17 (1) ◽  
pp. 83-86 ◽  
Author(s):  
James F. Nickel ◽  
John A. Gagnon ◽  
Leonard Levine
Keyword(s):  
Blood Pressure ◽  
Vascular Resistance ◽  
Sodium Excretion ◽  
Renal Vascular Resistance ◽  
Arterial Blood ◽  
Hind Limbs ◽  
Renal Changes ◽  
Anesthetized Dogs ◽  
Peripheral Trauma ◽  
Renal Vascular

Eight anesthetized dogs, given Clostridium perfringens type A toxic filtrate into the hind-limb muscles, showed severe spreading edema, hemoconcentration, marked reduction in para-aminohippurate (PAH) and creatinine clearances, and a rise in the renal vascular resistance. In the first 4 hr sodium excretion fell sharply, and mean arterial blood pressure, slightly. In eight similar dogs venous-occlusive pneumatic tourniquets were applied high on both hind limbs for 90 min. Edema was localized and minimal. Hematocrit was unchanged. PAH and creatinine clearances were extremely low in the second 30-min period of the occlusion but had risen somewhat in the last 30-min period. Sodium excretion was greatly reduced. Arterial pressure and vascular resistance rose very significantly. Upon removal of the tourniquets, PAH and creatinine clearances, blood pressure, and renal vascular resistance returned toward normal. Sodium excretion continued to fall. In many respects the renal changes resulting from two different forms of peripheral trauma are similar. Submitted on August 14, 1959

Abnormal Renal Haemodynamics and Renin Suppression in Hypertensive Patients

1970 ◽  
Vol 38 (1) ◽  
pp. 101-110 ◽  
Author(s):  
M. A. D. H. Schalekamp ◽  
M. P. A. Schalekamp-Kuyken ◽  
W. H. Birkenhäger
Keyword(s):  
Blood Pressure ◽  
Vascular Resistance ◽  
Renal Plasma Flow ◽  
Plasma Renin ◽  
Renal Vascular Resistance ◽  
Hypertensive Disease ◽  
Filtration Fraction ◽  
Plasma Renin Concentration ◽  
Renal Vascular ◽  
Intravascular Pressure

1. Intra-arterial pressure, renal plasma flow and glomerular filtration rate were estimated in thirty-two patients with benign essential hypertension. In twenty cases plasma renin concentrations were also determined. Variability of blood pressure was estimated by automatic indirect pressure recording. 2. There was an even distribution between high and low values of renal vascular resistance and filtration fraction. Variability of blood pressure was inversely related to renal vascular resistance. 3. In five patients plasma renin concentration was found to be abnormally low both in the recumbent and in the 45° tilt position. 4. Plasma renin concentration was related to renal blood flow, renal vascular resistance, filtration fraction and variability of blood pressure. 5. The results suggest that in hypertension renin release is suppressed by an increase in intravascular pressure at the level of the juxtaglomerularcells. The extent of renin suppression seems to be related to the stage of hypertensive disease.

Inhibition of ROMK blocks macula densa tubuloglomerular feedback yet causes renal vasoconstriction in anesthetized rats

2017 ◽  
Vol 312 (6) ◽  
pp. F1120-F1127 ◽  
Author(s):  
Magali Araujo ◽  
William J. Welch ◽  
Xiaoyan Zhou ◽  
Kathleen Sullivan ◽  
Shawn Walsh ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vascular Resistance ◽  
Renal Vascular Resistance ◽  
Tubuloglomerular Feedback ◽  
Volume Depletion ◽  
Renal Vasoconstriction ◽  
Compound C ◽  
Altered Blood ◽  
Renal Vascular ◽  
Dose Dependent

The Na+-K+-2Cl− cotransporter (NKCC2) on the loop of Henle is the site of action of furosemide. Because outer medullary potassium channel (ROMK) inhibitors prevent reabsorption by NKCC2, we tested the hypothesis that ROMK inhibition with a novel selective ROMK inhibitor (compound C) blocks tubuloglomerular feedback (TGF) and reduces vascular resistance. Loop perfusion of either ROMK inhibitor or furosemide caused dose-dependent blunting of TGF, but the response to furosemide was 10-fold more sensitive (IC50 = 10−6 M for furosemide and IC50 = 10−5 M for compound C). During systemic infusion, both diuretics inhibited TGF, but ROMK inhibitor was 10-fold more sensitive (compound C: 63% inhibition; furosemide: 32% inhibition). Despite blockade of TGF, 1 h of constant systemic infusion of both diuretics reduced the glomerular filtration rate (GFR) and renal blood flow (RBF) by 40–60% and increased renal vascular resistance (RVR) by 100–200%. Neither diuretic altered blood pressure or hematocrit. Proximal tubule hydrostatic pressures (PPT) increased transiently with both diuretics (compound C: 56% increase; furosemide: 70% increase) but returned to baseline. ROMK inhibitor caused more natriuresis (3,400 vs. 1,600% increase) and calciuresis (1,200 vs. 800% increase) but less kaliuresis (33 vs. 167% increase) than furosemide. In conclusion, blockade of ROMK or Na+-K+-2Cl− transport inhibits TGF yet increases renal vascular resistance. The renal vasoconstriction was independent of volume depletion, blood pressure, TGF, or PPT.

Intrarenal Formation of Angiotensin II in the Rat: Interference by Saralasin and SQ 20881

1974 ◽  
Vol 48 (s2) ◽  
pp. 37s-40s
Author(s):  
H. Zschiedrich ◽  
K. G. Hofbauer ◽  
E. Hackenthal ◽  
G. D. Baron ◽  
F. Gross
Keyword(s):  
Angiotensin Ii ◽  
Vascular Resistance ◽  
Plasma Renin ◽  
Rat Plasma ◽  
Renal Vascular Resistance ◽  
Angiotensin I ◽  
Renin Substrate ◽  
Vasoconstrictor Effect ◽  
Renal Vascular ◽  
Dose Dependent

1. Isolated rat kidneys were perfused with a medium free of components of the renin-angiotensin system. 2. Angiotensin II, angiotensin I, tetradecapeptide renin substrate or rat plasma renin substrate added to the medium caused a dose-dependent increase of renal vascular resistance. 3. The vasoconstrictor effect of angiotensin II was inhibited by 1-Sar-8-Ala-angiotensin II (Saralasin). The inhibition was dose-dependent, being complete at the highest doses applied. In this dose range, Saralasin increased renal vascular resistance. Saralasin also inhibited vasoconstriction induced by tetradecapeptide renin substrate. 4. The vasoconstrictor effect of angiotensin I was suppressed by SQ 20881, up to a maximum of 87% depending on the dose. Similarly the increase in renal vascular resistance induced by a purified preparation of rat plasma renin substrate was inhibited by 55%; no effect on the action of tetradecapeptide renin substrate was observed. 5. The data suggest that, within the kidney, angiotensin I is converted into angiotensin II to the extent of about 1.25%. Since no angiotensin I is formed from synthetic renin substrate, the vasoconstrictor effect of the tetradecapeptide may be either due to a direct interaction with the angiotensin II receptor or the consequence of the intrarenal formation of angiotensin II. In contrast, the results with rat plasma renin substrate suggest that angiotensin I is formed from ‘natural’ substrate and is subsequently converted into angiotensin II.

A renal vasodilator effect of angiotensin II revealed by dual thromboxane inhibition

1994 ◽  
Vol 72 (6) ◽  
pp. 632-636 ◽  
Author(s):  
Al-Hassan Badahman ◽  
Thomas W. Wilson
Keyword(s):  
Angiotensin Ii ◽  
Vascular Resistance ◽  
Renal Vascular Resistance ◽  
Sprague Dawley ◽  
Synthesis Inhibition ◽  
Renal Vasoconstriction ◽  
Sprague Dawley Rats ◽  
Renal Vascular ◽  
Arachidonate Release ◽  
Stimulation Of

Angiotensin II (AII) stimulates arachidonate release from renal endothelial and other ceils. Arachidonate is then metabolized by cyclooxygenase to prostaglandin (PG) H2, then PGI2 and thromboxane A2 (TXA2). PGH2 and TXA2 activate the same receptor and should augment AII-mediated vasoconstriction, whereas PGI2 is a vasodilator. We had previously shown that inhibiting TXA2 synthesis with furegrelate (FRG) redirects PGH2 metabolism toward PGI2, causing renal vasodilation. Because TXA2 synthesis inhibition may be incomplete and unmetabolized PGH2 may cause vasoconstriction, we reasoned that adding a PGH2/TXA2 receptor antagonist (BMS 180,290, formerly SQ 29548 (SQ)) to furegrelate should cause further renal vasodilation in the presence of AII Eight groups of 10 Sprague–Dawley rats received 120-min intravenous infusions of vehicle, FRG (2 mg∙kg−1 plus 2 mg∙kg−1∙h−1), SQ (2 mg∙kg−1 plus 2 mg∙kg−1∙h−1), FRG plus SQ, AII (10 ng∙kg−1∙min−1), AII plus FRG, AII plus SQ, or AII plus FRG plus SQ. Mean arterial pressure (MAP), p-[14C]aminohippurate clearance (CPAH), and [3H]insulin clearance were averaged for each rat for the final 90 min in three clearance periods. MAP did not change with any treatment. Estimating renal vascular resistance as MAP/CPAH confirmed a renal vasoconstrictor effect of this dose of AII: 58.1 ± 6.3 vs. 47.3 ± 6.8 (arbitrary units) with the vehicle (p < 0.05). FRG, SQ, or their combination did not affect renal vascular resistance, but adding FRG or SQ to AII prevented AII-mediated renal vasoconstriction. Adding both to AII caused net renal vasodilation to 24.8 ± 2.6 (p < 0.05 vs. vehicle). Inulin clearance changed in the same direction in all groups, but the changes were less marked. We conclude that stimulation of renal arachidonate release by AII combined with TXA2 synthesis inhibition and receptor antagonism results in vasodilation. This renal effect could be due to increased and unopposed renal vasodilator PG (principally PGI2) action.Key words: renal hemodynamics, angiotensin II, prostaglandins, thromboxane.

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