scholarly journals Enhanced sensitivity to acute angiotensin II is testosterone dependent in adult male growth-restricted offspring

2010 ◽  
Vol 298 (5) ◽  
pp. R1421-R1427 ◽  
Author(s):  
Norma B. Ojeda ◽  
Thomas P. Royals ◽  
Joshua T. Black ◽  
John Henry Dasinger ◽  
Jeremy M. Johnson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adult Male ◽  
Pressor Response ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Underlying Mechanism ◽  
Male Rats ◽  
Ang Ii ◽  
Enhanced Sensitivity ◽  
And Control

Placental insufficiency results in intrauterine growth restriction (IUGR) and hypertension in adult male growth-restricted rats. Although renal ANG II and plasma renin activity do not differ between growth-restricted and control rats, blockade of the renin-angiotensin system (RAS) abolishes hypertension in growth-restricted rats, suggesting that the RAS contributes to IUGR-induced hypertension. Moreover, castration abolishes hypertension in growth-restricted rats, indicating an important role for testosterone. Therefore, we hypothesized that enhanced responsiveness to ANG II contributes to hypertension in this model of IUGR and that androgens may play a pivotal role in this enhanced response. Physiological parameters were determined at 16 wk of age in male rats pretreated with enalapril (40 mg·kg−1·day−1) for 1 wk. Baseline blood pressures were similar between growth-restricted (112 ± 3 mmHg) and control (110 ± 2 mmHg) rats; however, an enhanced pressor response to acute ANG II (100 ng·kg−1·min−1 for 30 min) was observed in growth-restricted (160 ± 2 mmHg) vs. control (136 ± 2 mmHg; P < 0.05) rats. Castration abolished the enhanced pressor response to acute ANG II in growth-restricted (130 ± 2 mmHg) rats with no significant effect on blood pressure in controls (130 ± 2 mmHg). Blood pressure was increased to a similar extent above baseline in response to acute phenylephrine (100 μg/min) in control (184 ± 5 mmHg) and growth-restricted (184 ± 8 mmHg) rats, suggesting the enhanced pressor response in growth-restricted rats is ANG II specific. Thus, these results suggest that growth-restricted rats exhibit an enhanced responsiveness to ANG II that is testosterone dependent and indicate that the RAS may serve as an underlying mechanism in mediating hypertension programmed in response to IUGR.

Effects of modulation of renal kallikrein-kinin system in the nephrotic syndrome

1990 ◽  
Vol 258 (5) ◽  
pp. F1237-F1244
Author(s):  
F. N. Hutchison ◽  
V. I. Martin
Keyword(s):  
Blood Pressure ◽  
Enzyme Inhibitors ◽  
Pressor Response ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Ang Ii ◽  
Converting Enzyme Inhibitors ◽  
Kinin System ◽  
Renal Kallikrein ◽  
Kallikrein Kinin System

Albuminuria (UAlbV) can be reduced by converting-enzyme inhibitors (CEI), but the hormonal mechanism responsible for this effect has not previously been defined. Since CEI increase kinin activity as well as reduce angiotensin II (ANG II) activity, experiments were performed to determine the effect of isolated alterations in kinin and ANG II metabolism on UAlbV in rats with passive Heymann pephritis. Phosphoramidon was used to potentiate kinin activity without altering ANG II synthesis. Aprotinin was utilized in combination with the CEI, enalapril, to prevent the increase in kinin activity caused by CEI. UAlbV and the fractional renal clearance of albumin (FCAlb) decreased significantly after either phosphoramidon or enalapril, although only enalapril reduced blood pressure. Glomerular filtration rate (GFR) was not affected by either drug. Phosphoramidon did not affect plasma renin activity (PRA) or the pressor response to angiotensin I (ANG I), indicating that ANG II synthesis was not altered. Aprotinin prevented the reduction in UAlbV and FCAlb produced by CEI but not the hypotension, elevated PRA, or ANG I pressor blockade produced by CEI. Aprotinin alone had no effect on UAlbV, GFR, PRA, or blood pressure. UAlbV can be reduced by increasing kinin activity by a mechanism that is not dependent on suppression of ANG II activity or reduction in GFR or blood pressure. CEI may reduce proteinuria as a result of their action on the kallikrein-kinin system rather than on the renin-angiotensin system.

scholarly journals Early life stress induces renal dysfunction in adult male rats but not female rats

2013 ◽  
Vol 304 (2) ◽  
pp. R121-R129 ◽  
Author(s):  
Analia S. Loria ◽  
Tatsuo Yamamoto ◽  
David M. Pollock ◽  
Jennifer S. Pollock
Keyword(s):  
Blood Pressure ◽  
Adult Male ◽  
Early Life ◽  
Female Rats ◽  
Male Rats ◽  
Plasma Testosterone ◽  
Ang Ii ◽  
Control Female ◽  
Induced Hypertension ◽  
And Control

Maternal separation (MatSep) is a model of behavioral stress during early life. We reported that MatSep exacerbates ANG II-induced hypertension in adult male rats. The aims of this study were to determine whether exposure to MatSep in female rats sensitizes blood pressure to ANG II infusion similar to male MatSep rats and to elucidate renal mechanisms involved in the response in MatSep rats. Wistar Kyoto (WKY) pups were exposed to MatSep 3 h/day from days 2 to 14, while control rats remained with their mothers. ANG II-induced mean arterial pressure (MAP; telemetry) was enhanced in female MatSep rats compared with control female rats but delayed compared with male MatSep rats. Creatinine clearance (Ccr) was reduced in male MatSep rats compared with control rats at baseline and after ANG II infusion. ANG II infusion significantly increased T cells in the renal cortex and greater histological damage in the interstitial arteries of male MatSep rats compared with control male rats. Plasma testosterone was greater and estradiol was lower in male MatSep rats compared with control rats with ANG II infusion. ANG II infusion failed to increase blood pressure in orchidectomized male MatSep and control rats. Female MatSep and control rats had similar Ccr, histological renal analysis, and sex hormones at baseline and after ANG II infusion. These data indicate that during ANG II-induced hypertension, MatSep sensitizes the renal phenotype in male but not female rats.

Characterization of the renin-angiotensin system in the turtle Pseudemys scripta

1984 ◽  
Vol 247 (1) ◽  
pp. R15-R23 ◽  
Author(s):  
M. D. Cipolle ◽  
J. E. Zehr
Keyword(s):  
Pressor Response ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Ang Ii ◽  
Freshwater Turtles ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Fourfold Increase ◽  
Inactive Form ◽  
Pseudemys Scripta

Studies were conducted in freshwater turtles Pseudemys scripta to define some characteristics of the renin-angiotensin system in this reptile. Dialyzed acid-treated kidney extract (1 g tissue per ml water) produced a prolonged pressor response in unanesthetized turtles, which was eliminated by boiling the extract or by pretreating the turtle with [Sar1, Ile8]angiotensin II. A rat pressor assay was employed because turtle angiotensin (ANG) was bound poorly by the anti-[Asp1, Ile5, His9]ANG I used in our radioimmunoassay. Kidney extract incubated with homologous plasma (pH 5.5 and 25 degrees C) produced a time-dependent pressor response in rats. The pressor activity of the product was eliminated by dialysis or by pretreating the rats with [Sar1, Ile8]ANG II. The pressor response in anesthetized turtles to ANG I was significantly reduced by captopril, whereas the ANG II response remained unchanged, thus demonstrating the presence of ANG-converting enzyme activity in these animals. We determined the velocity of turtle ANG formation at various dilutions of enzyme (kidney extract) or substrate (plasma). Turtle kidney extract incubated with homologous plasma displayed typical Michaelis-Menten kinetics. Finally we conducted experiments to determine whether a portion of turtle plasma renin exists in an inactive form. Trypsinization caused a slight increase in plasma renin activity (PRA), whereas acidification to pH 3.3 yielded a fourfold increase in PRA.

Effect of ANG II receptor antagonist on albuminuria and renal function in passive Heymann nephritis

1992 ◽  
Vol 263 (2) ◽  
pp. F311-F318
Author(s):  
F. N. Hutchinson ◽  
S. K. Webster
Keyword(s):  
Blood Pressure ◽  
Receptor Antagonist ◽  
Enzyme Inhibitor ◽  
Pressor Response ◽  
Plasma Renin ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Heymann Nephritis

Angiotensin-converting enzyme inhibitors reduce albuminuria in nephrotic subjects, but the hormonal mechanism of this effect is not known. To determine whether specific inhibition of angiotensin (ANG) II activity would decrease albuminuria as occurs after converting enzyme inhibition, rats with passive Heymann nephritis received enalapril or the ANG II receptor antagonist losartan (6 mg.kg-1.day-1) for 4 days. Enalapril reduced both albuminuria (from 583 +/- 53 to 286 +/- 55 mg/day, P less than 0.001) and the fractional clearance of albumin (FCAlb) each day after starting treatment but did not affect glomerular filtration rate (GFR). Losartan reduced albuminuria significantly only after 4 days of treatment, but this value was not different from controls. GFR significantly increased with losartan (from 1.24 +/- 0.09 to 1.73 +/- 0.21 ml/min, P less than 0.05) so that FCAlb was reduced (from 0.0134 +/- 0.0027 to 0.0080 +/- 0.0018, P less than 0.05). Blood pressure decreased only in the enalapril group. Although plasma renin activity increased and the pressor response to ANG I was inhibited by both enalapril and losartan, suggesting effective peripheral blockade of ANG II activity, a third group of nephrotic rats was treated with losartan (18 mg.kg-1.day-1) to ensure that adequate ANG II blockade was achieved. Blood pressure decreased 10 mmHg, GFR increased from 1.35 +/- 0.14 to 1.79 +/- 0.12 ml/min (P less than 0.01), but albuminuria and FCAlb did not change. Urinary total kallikrein excretion was increased only in nephrotic rats treated with enalapril. Although both enalapril and losartan reduce ANG II activity, only the converting enzyme inhibitor reduces albuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary protein increases plasma renin and reduces pressor reactivity to angiotensin II

1986 ◽  
Vol 251 (1) ◽  
pp. F34-F39 ◽  
Author(s):  
M. S. Paller ◽  
T. H. Hostetter
Keyword(s):  
Angiotensin Ii ◽  
Dietary Protein ◽  
Pressor Response ◽  
Renin Angiotensin System ◽  
Chronic Administration ◽  
Plasma Renin ◽  
Prostaglandin Synthesis ◽  
Plasma Aldosterone ◽  
Ang Ii ◽  
Inhibition Of Prostaglandin Synthesis

The effect of dietary protein on the renin-angiotensin system was studied in rats. Rats were fed isocaloric, 50% (high protein, HP), or 6% (low protein, LP) protein diets with identical electrolyte content for 10 days. Food intake and electrolyte excretion were equivalent on the two diets. Plasma renin activity (PRA) was higher in HP (10.0 +/- 2.5 vs. 3.5 +/- 0.5 ng ANG I . ml-1 . h-1, P less than 0.02) as was plasma aldosterone. However, in conscious rats mean arterial pressure (MAP) was not different between groups. The pressor response to graded doses of angiotensin II (ANG II) was diminished by 30-60% with HP (all doses, P less than 0.05). ANG II binding by mesenteric artery smooth muscle particles did not differ between HP and LP. Chronic administration of captopril did not normalize the pressor response in HP. Urinary prostaglandin (PG) E and 6-keto-PGF1 alpha excretion was markedly increased by the HP diet. Acute inhibition of prostaglandin synthesis with meclofenamate restored the pressor response to ANG II in HP to that in LP. In summary, a HP diet increased PRA, plasma aldosterone, urinary PGE, and 6-keto-PGF1 alpha and decreased pressor responsiveness to ANG II. Resistance to ANG II was not reversed by chronic converting enzyme inhibition but was abolished by inhibition of prostaglandin synthesis.

Prostacyclin attenuates both the pressor and adrenocortical response to angiotensin II in human pregnancy

1989 ◽  
Vol 76 (5) ◽  
pp. 529-534 ◽  
Author(s):  
F. Broughton Pipkin ◽  
R. Morrison ◽  
P. M. S. O'Brien
Keyword(s):  
Angiotensin Ii ◽  
Diastolic Pressure ◽  
Pressor Response ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Normal Pregnancy ◽  
Ang Ii ◽  
Angiotensin System ◽  
Basal Plasma ◽  
Second Trimester Pregnancy

1. The effects of angiotensin II (ANG II) infusion without and with simultaneous infusion of prostacyclin (PGI2; 1.4 pmol min−1 kg−1; 5 ng min−1 kg−1) have been studied in 16 women in second-trimester pregnancy. Ten received one infusion of ANG II alone, followed by its infusion together with PGI2; the remainder received two identical infusions of ANG II alone as controls. 2. PGI2 administration was associated with a small fall in diastolic pressure (P < 0.01) and a proportionally greater rise in heart rate (P < 0.001). Small rises in basal plasma renin and ANG II concentrations and a fall in aldosterone concentration were not statistically significant. 3. The diastolic pressor response to ANG II was blunted during PGI2 infusion by comparison with controls (P < 0.025); this diminution in response was greatest in patients who had initially been most sensitive to ANG II (P < 0.02). 4. The evoked increment in plasma aldosterone during ANG II infusion was considerably reduced (P < 0.005) in the presence of PGI2. 5. These data further support the hypothesis of a role for PGI2 in relation to the blunted pressor response to ANG II of normal pregnancy. The apparent inhibitory effects of PGI2 on aldosterone secretion may partly explain the previously described dissociation between the renin-angiotensin system and aldosterone in pregnancy.

Angiotensin II Blockade during Combined Thiazide—β-Adrenoreceptor-Blocker Treatment

1979 ◽  
Vol 57 (s5) ◽  
pp. 123s-125s ◽  
Author(s):  
H. Ibsen ◽  
A. Leth ◽  
A. McNair ◽  
J. Giese
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Diastolic Blood Pressure ◽  
Plasma Volume ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Close Correlation ◽  
Ang Ii ◽  
Arterial Blood ◽  
Change In Mean

1. Sixteen patients (11 male, five female), median age 41 years, with essential hypertension insufficiently controlled by hydrochlorothiazide (75 mg/day; diastolic blood pressure ≥ 100 mmHg), were studied. 2. Plasma renin concentration [renin], plasma angiotensin II concentration ([ANG II]), plasma volume and exchangeable sodium (NaE) were determined, and a saralasin infusion (5·4 nmol min−1 kg−1) was carried out while the patients were on thiazide alone and, in 14 cases, 3 months after addition of a β-adrenoreceptor blocker (propranolol, six, metoprolol, six, and atenolol, two patients). 3. On thiazide alone, saralasin caused a significant decrease in mean arterial blood pressure in 12 out of 16 patients. The saralasin response was closely related to pre-saralasin plasma [ANG II] (r = −0·73, P &lt; 0·01). Plasma [renin] and [ANG II] were higher than normal in the group as a whole. 4. After addition of a β-adrenoreceptor blocker systolic and diastolic blood pressure decreased from 164/109 mmHg to 136/94 mmHg. Plasma [renin] and [ANG II] decreased by 40 and 58% respectively. At this point, saralasin caused no significant change in mean arterial pressure. No close correlation was found between plasma [renin] or [ANG II] or saralasin response on thiazide treatment and changes in blood pressure during subsequent thiazide/β-adrenoreceptor-blocker treatment. Plasma volume and NaE did not change significantly. 5. In patients with thiazide-induced stimulation of the renin—angiotensin system, addition of a β-adrenoreceptor blocker leads to suppression of the system and, at the same time, ANG II-dependence of blood pressure disappears. This contributes to the antihypertensive effect of β-adrenoreceptor blockers in this particular situation.

Increased dietary sodium alters neural control of blood pressure during intravenous ANG II infusion

2003 ◽  
Vol 284 (2) ◽  
pp. H559-H565 ◽  
Author(s):  
Steven L. Bealer
Keyword(s):  
Blood Pressure ◽  
Neural Control ◽  
Tap Water ◽  
Pressor Response ◽  
Isotonic Saline ◽  
Dietary Sodium ◽  
Male Rats ◽  
Ang Ii ◽  
Blood Pressure Responses

Increased dietary sodium enhances both excitatory and inhibitory blood pressure responses to stimulation of the central sympathetic nervous system (SNS) centers. In addition, long-term (hours to days) administration of ANG II increases blood pressure by activation of the SNS. These studies investigated the effects of increased dietary sodium on SNS control of blood pressure during 0- to 24-h infusion of ANG II in conscious, male rats consuming either tap water or isotonic saline (Iso) for 2 to 3 wk. The SNS component (evaluated by ganglionic blockade with trimetaphan) of both control blood pressure and the pressor response to intravenous ANG II was reduced in Iso animals. Furthermore, although the pressor response to intravenous ANG II infusion was similar between groups, the baroreflex-induced bradycardia during the initial 6 h of ANG II infusion was significantly greater, whereas the tachycardia accompanying longer infusion periods was significantly attenuated in Iso animals. These data suggest that in normal rats increased dietary sodium enhances sympathoinhibitory responses during intravenous ANG II.

scholarly journals Estrogen protects transgenic hypertensive rats by shifting the vasoconstrictor-vasodilator balance of RAS

1997 ◽  
Vol 273 (6) ◽  
pp. R1908-R1915 ◽  
Author(s):  
K. Bridget Brosnihan ◽  
Ping Li ◽  
Detlev Ganten ◽  
Carlos M. Ferrario
Keyword(s):  
Replacement Therapy ◽  
Estrogen Replacement Therapy ◽  
Pressor Response ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Cardiovascular Responses ◽  
Estrogen Treatment ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Estrogen Replacement

In pursuit of the hypothesis that estrogen shifts the vasoconstrictor-vasodilator balance of the renin-angiotensin system, we investigated the cardiovascular responses to administration of angiotensin-(1—7) [ANG-(1—7)] and angiotensin II (ANG II) in female transgenic (mRen2)27-positive [Tg(+)] and -negative [Tg(−)] rats in the presence and absence of 3 wk of estrogen replacement therapy. Fifty-three female Tg(−) and Tg(+) rats were oophorectomized and received either 17β-estradiol (1.5 mg/rat sc for 3 wk) or vehicle. At the end of 3 wk of estrogen treatment, mean blood pressure was lowered in freely moving chronically cannulated Tg(+) (159 ± 4 vs. 145 ± 5 mmHg, P < 0.05) and Tg(−) (119 ± 4 vs. 108 ± 2 mmHg, P < 0.05) rats. Moreover, the magnitude of the depressor component of the biphasic response to ANG-(1—7) was significantly enhanced in estrogen-treated Tg(+) rats, whereas the pressor component to ANG-(1—7) was attenuated in both Tg(+) and Tg(−) rats. Estrogen replacement significantly attenuated the pressor response to ANG II in both Tg(+) and Tg(−) rats. In addition, estrogen replacement therapy significantly reduced plasma ANG-converting enzyme activity in association with a reduction in circulating levels of ANG II. Tissue levels (kidney and aorta) of ANG-converting enzyme were also reduced with chronic estrogen replacement therapy. On the other hand, estrogen augmented the levels of plasma ANG-(1—7) in Tg(+) animals. Plasma renin activity was unchanged with estrogen treatment. These findings provide the first evidence demonstrating that estrogen is protective against hypertension, possibly by amplifying the vasodilator contributions of ANG-(1—7), while reducing the formation and vasoconstrictor actions of ANG II.

NG-monomethyl-L-arginine and nitroarginine potentiate pressor responsiveness of vasoconstrictors in conscious rats

1992 ◽  
Vol 262 (6) ◽  
pp. R1137-R1144 ◽  
Author(s):  
K. P. Conrad ◽  
S. L. Whittemore
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Pressor Response ◽  
Renin Angiotensin System ◽  
Rat Aorta ◽  
Bolus Administration ◽  
Ang Ii ◽  
Baseline Blood Pressure ◽  
Conscious Rats ◽  
Pressor Responses

NG-monomethyl-L-arginine (NMA) and nitroarginine have been reported to be competitive inhibitors of the production of endothelium-derived relaxing factor (EDRF). In chronically instrumented conscious rats, we observed that the pressor response of NMA was attenuated by pretreatment with L-arginine but not by pretreatment with D-arginine, phentolamine, or meclofenamate. Inhibitors of the renin-angiotensin system, captopril and [Sar1,Ile5,Thr8]angiotensin II, did not significantly affect the pressor response of NMA, either. Ten to fifteen minutes after bolus administration of 7-15 mg/kg NMA, when baseline blood pressure was virtually restored, the pressor responses of angiotensin II (ANG II), norepinephrine, and arginine vasopressin were significantly potentiated by approximately 30-40% compared with control values. This potentiation was prevented by pretreatment with L- but not D-arginine. It was also observed in conscious rats subjected to ganglionic blockade. Likewise, the pressor responses of ANG II were significantly increased during infusions of 2 and 5 micrograms/min nitroarginine methyl ester (NAME), dosages that raised baseline blood pressure by 6 +/- 2 and 15 +/- 3 mmHg, respectively. During administration of 5 and 50 micrograms/min NAME, hypotensive responses of methacholine and histamine were only modestly attenuated compared with the responses recorded during infusions of phenylephrine, which raised resting blood pressure to comparable levels. Finally, in freshly isolated rat aorta, NMA inhibited basal and stimulated production of guanosine 3',5'-cyclic monophosphate in a manner comparable to reduced hemoglobin, a known inhibitor of EDRF.(ABSTRACT TRUNCATED AT 250 WORDS)

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