scholarly journals Plasminogen Deficiency and Amiloride Mitigate Angiotensin II–Induced Hypertension in Type 1 Diabetic Mice Suggesting Effects Through the Epithelial Sodium Channel

2020 ◽  
Vol 9 (23) ◽  
Author(s):  
Henrik Andersen ◽  
Maria Høj Hansen ◽  
Kristian B. Buhl ◽  
Mette Stæhr ◽  
Ulla G. Friis ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Angiotensin Ii ◽  
Sodium Channel ◽  
Arterial Blood Pressure ◽  
Epithelial Sodium Channel ◽  
Diabetic Mice ◽  
Wild Type ◽  
Arterial Blood ◽  
Prorenin Receptor

Background Diabetic nephropathy is a common diabetes mellitus complication associated with hypertension, proteinuria, and excretion of urinary plasmin that activates the epithelial sodium channel, ENaC, in vitro . Here we hypothesized that the deletion of plasminogen and amiloride treatment protect against hypertension in diabetes mellitus. Methods and Results Male plasminogen knockout (plasminogen‐deficient [Plg −/− ]) and wild‐type mice were rendered diabetic with streptozotocin. Arterial blood pressure was recorded continuously by indwelling catheters before and during 10 days of angiotensin II infusion (ANGII; 30–60 ng/kg per minute). The effect of amiloride infusion (2 mg/kg per day, 4 days) was tested in wild‐type, diabetic ANGII‐treated mice. Streptozotocin increased plasma and urine glucose concentrations and 24‐hour urine albumin and plasminogen excretion. Diabetic Plg −/− mice displayed larger baseline albuminuria and absence of urine plasminogen. Baseline mean arterial blood pressure did not differ between groups. Although ANGII elevated blood pressure in wild‐type, diabetic wild‐type, and Plg −/− control mice, ANGII did not change blood pressure in diabetic Plg −/− mice. Compared with ANGII infusion alone, wild‐type ANGII‐infused diabetic mice showed blood pressure reduction upon amiloride treatment. There was no difference in plasma renin, ANGII, aldosterone, tissue prorenin receptor, renal inflammation, and fibrosis between groups. Urine from wild‐type mice evoked larger amiloride‐sensitive current than urine from Plg −/− mice with or without diabetes mellitus. Full‐length γ‐ENaC and α‐ENaC subunit abundances were not changed in kidney homogenates, but the 70 kDa γ‐ENaC cleavage product was increased in diabetic versus nondiabetic mice. Conclusions Plasmin promotes hypertension in diabetes mellitus with albuminuria likely through the epithelial sodium channel.

PS 07-29 FLAVONE DERIVATIVE, CSH-3-124 DECREASES ARTERIAL BLOOD PRESSURE THROUGH INHIBITION OF ANGIOTENSIN II

2016 ◽  
Vol 34 (Supplement 1) ◽  
pp. e291
Author(s):  
Seon-Ah Jin ◽  
Hee jung Seo ◽  
Sun Kyeong Kim ◽  
Gyu Yong Song ◽  
Jin-Ok Jeong
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Arterial Blood Pressure ◽  
Arterial Blood ◽  
Flavone Derivative

Role of arteria baroreceptor input on thirst and urinary responses to intracerebroventricular angiotensin II

1993 ◽  
Vol 265 (3) ◽  
pp. R591-R595 ◽  
Author(s):  
R. L. Thunhorst ◽  
S. J. Lewis ◽  
A. K. Johnson
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Arterial Blood Pressure ◽  
Water Intake ◽  
Enzyme Inhibitor ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Arterial Blood ◽  
Endogenous Formation

Intracerebroventricular (icv) infusion of angiotensin II (ANG II) in rats elicits greater water intake under hypotensive, compared with normotensive, conditions. The present experiments used sinoaortic baroreceptor-denervated (SAD) rats and sham-operated rats to examine if the modulatory effects of arterial blood pressure on water intake in response to icv ANG II are mediated by arterial baroreceptors. Mean arterial blood pressure (MAP) was raised or lowered by intravenous (i.v.) infusions of phenylephrine (1 or 10 micrograms.kg-1 x min-1) or minoxidil (25 micrograms.kg-1 x min-1), respectively. The angiotensin-converting enzyme inhibitor captopril (0.33 mg/min) was infused i.v. to prevent the endogenous formation of ANG II during testing. Urinary excretion of water and solutes was measured throughout. Water intake elicited by icv ANG II was inversely related to changes in MAP. Specifically, rats drank more water in response to icv ANG II when MAP was reduced by minoxidil but drank less water when MAP was elevated by phenylephrine. The influence of changing MAP on the icv ANG II-induced drinking responses was not affected by SAD. These results suggest that the modulatory effects of arterial blood pressure on icv ANG II-induced drinking can occur in the absence of sinoaortic baroreceptor input.

Effect of Sodium Depletion on the Steroidogenic and Pressor Actions of Angiotensin in the Rat

1979 ◽  
Vol 56 (4) ◽  
pp. 325-333 ◽  
Author(s):  
W. B. Campbell ◽  
J. M. Schmitz ◽  
H. D. Itskovitz
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
Sodium Depletion ◽  
Angiotensin I ◽  
Arterial Blood ◽  
Serum Aldosterone ◽  
Pressor Responses ◽  
Angiotensin Iii

1. To investigate the relative roles of angiotensin II (AII) and des-Asp1-angiotensin II (angiotensin III) in the control of blood pressure and aldosterone release, the effects of seven angiotensin agonists on mean arterial blood pressure and serum aldosterone concentrations were compared in normal and sodium-depleted, conscious rats. 2. In normal rats, angiotensin I, α-Asp1-angiotensin II, β-Asp1-angiotensin II, and angiotensin II-amide were equipotent in elevating mean arterial blood pressure. Angiotensin III, des-Asp1-angiotensin I, and poly-O-acetylserine-angiotensin II were 25%, 25%, and 41% as potent as angiotensin II, respectively. After sodium depletion, pressor responses to these angiotensin peptides were reduced approximately 60–80% when compared with control responses. In contrast, pressor responses to noradrenaline were not significantly affected by sodium depletion. 3. Angiotensin II, β-Asp1-angiotensin II, angiotensin II-amide, and angiotensin III were equipotent in increasing serum aldosterone concentrations in normal animals. Angiotensin I was 59% and des-Asp1-angiotensin I only 5% as potent as angiotensin II in their abilities to release aldosterone. After sodium depletion, control serum aldosterone concentrations increased as did the slope of the dose—response curve for each angiotensin peptide. Angiotensin II was the most potent steroidogenic peptide in sodium-depleted rats with angiotensin III and β-Asp1-angiotensin II being 27%, angiotensin I 7%, angiotensin II-amide 3%, and des-Asp1-angiotensin I 1% as potent as angiotensin II in releasing aldosterone. Poly-O-acetylserine-angiotensin II has less steroidogenic effect than angiotensin II or III in both normal and sodium-depleted animals. 4. Infusions of the angiotensin II antagonist, Sar1-Ile8-angiotensin II, and the angiotensin III antagonist, Ile7-angiotensin III, enhanced aldosterone release in normal rats without altering blood pressure. After sodium depletion, Sar1-Ile8-angiotensin II decreased blood pressure without affecting aldosterone release whereas Ile7-angiotensin III diminished aldosterone release without altering blood pressure. 5. These data suggest that angiotensin II, independent of its conversion into angiotensin III, is an important regulator of steroidogenesis in the rat in normal sodium states. In sodium depletion, the octapeptide retains significant steroidogenic activity; however, the contribution of angiotensin III to its steroidogenic effects is increased.

Support of arterial blood pressure by major pressor systems in conscious dogs

1988 ◽  
Vol 255 (3) ◽  
pp. H483-H491 ◽  
Author(s):  
P. H. Brand ◽  
P. J. Metting ◽  
S. L. Britton
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Steady State ◽  
Autonomic Nervous System ◽  
Angiotensin Ii ◽  
Arterial Blood Pressure ◽  
Autonomic Function ◽  
Autonomic Ganglia ◽  
Arterial Blood

The roles of the autonomic nervous system, vasopressin, and angiotensin II in support of blood pressure were evaluated in seven conscious, resting dogs while hydrated or dehydrated. Mean arterial blood pressure (MAP) was monitored, and the dogs were given hexamethonium to block autonomic ganglia. Thirty minutes later, they were given captopril, and after another 30 min, a vasopressin V1 antagonist, d(CH2)5TyrMeAVP, was given. The order okf administration of captopril and d(CH2)5TyrMeAVP was alternated in different experiments. Hexamethonium had no effect on steady-state MAP in either hydrated or dehydrated dogs. In hydrated dogs, the average MAP was 100 mmHg; d(CH2)5TyrMeAVP decreased MAP by approximately 12 mmHg, and captopril decreased MAP by 24 mmHg. The magnitude of the effect of these two inhibitors was independent of the order of their administration. Dehydration doubled the effect of d(CH2)5TyrMeAVP on MAP but had no effect on the response to captopril. The results suggest that 1) autonomic function is not essential for maintenance of arterial blood pressure in resting dogs; 2) during autonomic ganglionic blockade, arterial blood pressure is supported by both angiotensin II and vasopressin; and 3) dehydration increases the role of vasopressin in control of blood pressure.

Centrally Mediated Effects of Sodium and Angiotensin II on Arterial Blood Pressure and Fluid Balance

1972 ◽  
Vol 85 (3) ◽  
pp. 398-407 ◽  
Author(s):  
B. Andersson ◽  
L. Eriksson ◽  
O. Fernández ◽  
C.-G. Kolmodin ◽  
R. Oltner
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Arterial Blood Pressure ◽  
Fluid Balance ◽  
Mediated Effects ◽  
Arterial Blood
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