MO093CLARIFICATION OF BIOSYNTHESIS OF ANGIOPROTECTIN

Abstract Background and Aims The renin-angiotensin-aldosterone system (RAAS) is involved in the regulation of the blood pressure, water- and electrolyte balance. Pathophysiologically, this system is essential for the development and pathogenesis of both cardiovascular and renal diseases. Recently, the angiotensin peptide ´angioprotectin´ was identified as an antagonist of the contractile effect of angiotensin II. The amino acid sequence of angioprotectin (pro-glu-val-tyr-ile-his-pro-phe) compared to the amino acid sequence of angiotensin II (asp-arg-val-tyr-ile-his-pro-phe) differs in the n-terminal amino acids asp1 and arg2, which are transformed to pro1 and glu2 by endothelial cells (Jankowski et al., 2011). The aim of the study is the identification of the underlying mechanism of the transformation of angiotensin II to angioprotectin. Method To clarify the transformation of angioprotectin diverse angiotensin peptides were incubated with enzymes like glutamic oxaloacetic transaminase (GOT), cofactors like pyridoxal-5’-phosphate (PLP) and other substances like vitamin B6-derivates. Aliquots were collected time-dependently and analyzed by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF). To investigate the impact of angioprotectin on the organism, rats were treated with angiotensin II in the absence and presence of PLP. The blood pressure was used as read-out of the effect of the treatment. Results The incubation of angiotensin II with pyridoxal-5’-phosphate in vitro caused in increased amount of angioprotectin. Since the first two amino acids aspartic acid and arginine of further peptides like angiotensin I, angiotensin (1-6) and cortistatin-17 were also metabolized to proline and glutamic acid, the underlying mechanism is not specific for angiotensin II, but for aspartic acid and arginine. In accordance with this, the blood pressure of spontaneously hypertensive rats (SHR) treated with PLP decreases after three days. The blood pressure of Wistar Kyoto rats (WKY) treated with angiotensin II increases, whereas the blood pressure of WKY rats treated with angiotensin II and PLP decreases to normal level. Conclusion Angiotensin II is obviously metabolized by pyridoxal-5’-phosphate (PLP) to angioprotectin. PLP decreases the blood pressure in spontaneously hypertensive rats and in Wistar Kyoto rats. The first two amino acids aspartic acid and arginine are also metabolized to proline and glutamic acid in other peptides.

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The effect of prolonged infusion and withdrawal of angiotensin II in the spontaneously hypertensive rat

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y86-126 ◽

1986 ◽

Vol 64 (6) ◽

pp. 748-750 ◽

Cited By ~ 4

Author(s):

Edward K. Y. Chiu ◽

J. Robert McNeill

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Spontaneously Hypertensive Rats ◽

Spontaneously Hypertensive Rat ◽

Hypertensive Rats ◽

Prolonged Infusion ◽

Spontaneously Hypertensive ◽

Control Value ◽

Arterial Blood ◽

Wistar Kyoto

In spontaneously hypertensive rats (SHR) and their normotensive Wistar–Kyoto controls (WKY), prolonged intravenous administration of angiotensin II (AII, 0.2 μg∙kg−1∙min−1 for 3 h) resulted in similar increases in arterial blood pressure. Heart rate decreased in WKY and increased in SHR. At the end of the infusion, blood pressure dropped substantially in SHR, but not in WKY: at 5 h after AII withdrawal, blood pressure in SHR had fallen from a control value of 172 ± 3.3 to 146 ± 3.9 mmHg (p < 0.01), whereas pressure in WKY had fallen from 116 ± 3.0 to 107 ± 4.2 mmHg (statistically non significant). Thus, pressure at 5 h after AII withdrawal was still substantially higher (p < 0.01) in the SHR than in the WKY. The results demonstrate that the fall in blood pressure following withdrawal of a prolonged infusion of AII in SHR is much less than that reported to occur following withdrawal of a prolonged infusion of vasopressin (AVP) in SHR.

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Effects of dietary Ca2+ on erythrocyte Na+-transport systems in spontaneously hypertensive rats

Clinical Science ◽

10.1042/cs0810107 ◽

1991 ◽

Vol 81 (1) ◽

pp. 107-112 ◽

Cited By ~ 5

Author(s):

K. Fujito ◽

M. Yokomatsu ◽

N. Ishiguro ◽

H. Numahata ◽

Y. Tomino ◽

...

Keyword(s):

Blood Pressure ◽

Spontaneously Hypertensive Rats ◽

Transport Systems ◽

Hypertensive Rats ◽

Na Transport ◽

Spontaneously Hypertensive ◽

Na Pump ◽

Wistar Kyoto ◽

Increased Activity ◽

Regulation Of Blood Pressure

1. The purpose of this study was to determine the effect of dietary Ca2+ intake on blood pressure and erythrocyte Na+ transport in spontaneously hypertensive rats. 2. Spontaneously hypertensive rats and Wistar-Kyoto rats were fed diets with three different Ca2+ contents, 0.1% (low-Ca2+ diet), 0.6% (normal-Ca2+ diet) and 4.0% (high-Ca2+ diet), between 6 and 20 weeks of age. At 20 weeks of age, the levels of erythrocyte Na+ efflux, as well as Na+ and K+ contents in erythrocytes, were measured. 3. On the low-Ca2+ diet, spontaneously hypertensive rats showed an enhancement of hypertension. Conversely, on the high-Ca2+ diet, they showed an attenuation of the increase in blood pressure. Spontaneously hypertensive rats had a lower erythrocyte Na+ content and increased activity of the Na+ pump at higher levels of dietary Ca2+. Passive Na+ permeability and Na+-K+ co-transport were similar in spontaneously hypertensive rats on the low-, normal- and high-Ca2+ diets. There were no significant differences in blood pressure and in Na+ pump activity in WKY on the three different diets. 4. It is concluded that dietary Ca2+ might affect the regulation of blood pressure in spontaneously hypertensive rats by changing the activity of Na+ pump in the cell membrane.

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Metformin decreases plasma insulin levels and systolic blood pressure in spontaneously hypertensive rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1994.267.4.h1250 ◽

1994 ◽

Vol 267 (4) ◽

pp. H1250-H1253 ◽

Cited By ~ 5

Author(s):

S. Verma ◽

S. Bhanot ◽

J. H. McNeill

Keyword(s):

Blood Pressure ◽

Systolic Blood Pressure ◽

Spontaneously Hypertensive Rats ◽

Plasma Insulin ◽

Metformin Treatment ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Insulin Levels ◽

Plasma Insulin Levels ◽

Wistar Kyoto

To determine the relationship between hyperinsulinemia and hypertension in spontaneously hypertensive rats (SHR), the antihyperglycemic agent metformin was administered to SHR and their Wistar-Kyoto (WKY) controls, and its effects on plasma insulin levels and blood pressure were examined. Five-week-old rats were started on oral metformin treatment (350 mg.kg-1.day-1, which was gradually increased to 500 mg.kg-1.day-1 over a 2-wk period). Metformin treatment caused sustained decreases in plasma insulin levels in the SHR (27.1 +/- 2.3 vs. untreated SHR 53.5 +/- 2.7 microU/ml, P < 0.001) without having any effect in the WKY (30.7 +/- 2.2 vs. untreated WKY 37.8 +/- 1.6 microU/ml, P > 0.05). The treatment did not affect the plasma glucose levels in any group. Metformin treatment also attenuated the increase in systolic blood pressure in the SHR (157 +/- 6.0 vs. untreated SHR 196 +/- 9.0 mmHg, P < 0.001) but had no effect in the WKY (134 +/- 3 vs. untreated WKY 136 +/- 4 mmHg, P > 0.05). Furthermore, raising plasma insulin levels in the metformin-treated SHR to levels that existed in the untreated SHR reversed the effect of metformin on blood pressure (189 +/- 3 vs. untreated SHR 208 +/- 5.0 mmHg, P > 0.05). These findings suggest that either hyperinsulinemia may contribute toward the increase in blood pressure in the SHR or that the underlying mechanism is closely associated with the expression of both these disorders.

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Contribution of Vascular Nitric Oxide to Basal Blood Pressure in Conscious Spontaneously Hypertensive Rats and Normotensive Wistar Kyoto Rats

Clinical Science ◽

10.1042/cs0890177 ◽

1995 ◽

Vol 89 (2) ◽

pp. 177-182 ◽

Cited By ~ 31

Author(s):

Naoyoshi Minami ◽

Yutaka Imai ◽

Jun-Ichiro Hashimoto ◽

Keishi Abe

Keyword(s):

Nitric Oxide ◽

Blood Pressure ◽

Mean Arterial Pressure ◽

Methyl Ester ◽

Spontaneously Hypertensive Rats ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Wistar Kyoto Rats ◽

Basal Blood Pressure ◽

Wistar Kyoto

1. The aim of this study was to clarify the extent to which vascular nitric oxide contributes to basal blood pressure in conscious spontaneously hypertensive rats and normotensive Wistar Kyoto rats. 2. The contribution of vascular nitric oxide to maintenance of blood pressure was estimated by measuring the pressor response to an intravenous injection of nitric oxide synthase inhibitor, Nω-l-arginine methyl ester, given after serial injections of captopril, vasopressin V1-receptor antagonist (V1-antagonist) and ganglion blocker (pentolinium) in conscious spontaneously hypertensive and Wistar Kyoto rats aged 20–28 weeks. To estimate the ‘amplifier property’ of hypertrophied vasculature in spontaneously hypertensive rats, which is known to modulate pressor responses, the lower blood pressure plateau after serial injections of captopril, V1-antagonist and pentolinium and the maximum blood pressure elicited by subsequent injection of increasing doses of phenylephrine were also measured. 3. The serial injections of captopril, V1-antagonist and pentolinium decreased mean arterial pressure from 164 ± 9 mmHg to 67 ± 2 mmHg and from 117 ± 2 mmHg to 49 ± 1 mmHg in spontaneously hypertensive and Wistar Kyoto rats respectively. The subsequent injection of Nω-l-arginine methyl ester restored mean arterial pressure almost to its control levels in both spontaneously hypertensive and Wistar Kyoto rats. The absolute changes in mean arterial pressure elicited by Nω-l-arginine methyl ester were significantly greater in spontaneously hypertensive than in Wistar Kyoto rats (P < 0.01), but there was no significant difference in the responses to Nω-l-arginine methyl ester when they were expressed as percentages of either the lower blood pressure plateau or maximum blood pressure. 4. These results indicate that basal blood pressure in both spontaneous hypertensive and Wistar Kyoto rats is maintained by a balance between vascular nitric oxide and major pressor systems. They also suggest that the vasodilatory effect of vascular nitric oxide does not differ between spontaneously hypertensive and Wistar Kyoto rats, and that the increased pressor effect of Nω-l-arginine methyl ester in spontaneously hypertensive rats is due to a vascular amplifier mechanism.

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Ca2+ sensitization and Ca2+ entry in the control of blood pressure and adrenergic vasoconstriction in conscious Wistar–Kyoto and spontaneously hypertensive rats

Journal of Hypertension ◽

10.1097/hjh.0b013e328362adb3 ◽

2013 ◽

Vol 31 (10) ◽

pp. 2025-2035 ◽

Cited By ~ 14

Author(s):

Michal Behuliak ◽

Mária Pintérová ◽

Michal Bencze ◽

Miriam Petrová ◽

Silvia Líšková ◽

...

Keyword(s):

Blood Pressure ◽

Spontaneously Hypertensive Rats ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Wistar Kyoto

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Hypertension transmitted by kidneys from stroke-prone spontaneously hypertensive rats

AJP Renal Physiology ◽

10.1152/ajprenal.1989.257.2.f197 ◽

1989 ◽

Vol 257 (2) ◽

pp. F197-F203 ◽

Cited By ~ 4

Author(s):

R. Rettig ◽

H. Stauss ◽

C. Folberth ◽

D. Ganten ◽

B. Waldherr ◽

...

Keyword(s):

Blood Pressure ◽

Renal Transplantation ◽

Spontaneously Hypertensive Rats ◽

Plasma Renin ◽

F1 Hybrids ◽

Hypertensive Rats ◽

Plasma Urea ◽

Spontaneously Hypertensive ◽

Major Function ◽

Wistar Kyoto

We determined whether transplantations of kidneys from stroke-prone spontaneously hypertensive rats (SPSHR) and from normotensive Wistar-Kyoto rats (WKY) alter blood pressure in renal graft recipients. Kidneys taken from seven male SPSHR and seven male WKY rats (blood pressure 186 +/- 4.8 and 111 +/- 3.7 mmHg, respectively) at the age of 20 wk were transplanted, using microsurgical techniques, to bilaterally nephrectomized age-matched male F1 hybrids (blood pressure 136 +/- 2.6 and 138 +/- 6.3 mmHg, respectively) bred from SPSHR and WKY parents. After renal transplantation, blood pressure in recipients of SPSHR kidneys rose to 146 +/- 11.8 (week 2), 163 +/- 16.4 (week 3), 192 +/- 17.1 (week 4), 222 +/- 17.7 (week 5), 221 +/- 12.6 (week 6), 218 +/- 20.3 (week 7), and 239 +/- 9.2 mmHg (week 8). There was no significant change in blood pressure in recipients of WKY kidneys. All rats recovered rapidly from surgery. After renal transplantation, there was a significant increase in daily water intake, a decrease in plasma renin activity, and a slight rise in plasma urea concentration. Our data show that transplantation of kidneys from adult SPSHR causes hypertension in normotensive recipients, indicating a major function for the kidney in SPSHR hypertension.

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Duration of Electrically Induced Atrial Fibrillation Is Augmented by High Voltage of Stimulus with Higher Blood Pressure in Hypertensive Rats

International Journal of Hypertension ◽

10.1155/2014/980505 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Tomomi Nagayama ◽

Yoshitaka Hirooka ◽

Akiko Chishaki ◽

Masao Takemoto ◽

Yasushi Mukai ◽

...

Keyword(s):

Atrial Fibrillation ◽

Blood Pressure ◽

Arterial Pressure ◽

High Voltage ◽

Spontaneously Hypertensive Rats ◽

Low Voltage ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

High Stimulus ◽

Wistar Kyoto

Objective.Many previous clinical studies have suggested that atrial fibrillation (AF) is closely associated with hypertension. However, the benefits of antihypertensive therapy on AF are still inconsistent, and it is necessary to explore the factors augmenting AF in hypertensive rats. The aim of the present study was to investigate the correlation between arterial pressure or voltage stimulus and to the duration of electrically induced AF in normotensive or hypertensive rats.Methods.AF was reproducibly induced by transesophageal atrial burst pacing in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). We did the burst pacing at high (20 V) or low (5 V) voltage.Results.Duration of AF did not correlate with systolic blood pressure (SBP) and stimulus voltage in WKY. However, only in SHR, duration of AF with high stimulus voltage significantly correlated with SBP and was significantly longer in high than in low voltage stimulus.Discussion and Conclusion.Duration of AF is augmented by high voltage stimulus with higher blood pressure in SHR.

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