Synergistic Effects of ACE Inhibition and Ang II Antagonism on Blood Pressure, Cardiac Weight, and Renin in Spontaneously Hypertensive Rats

48 Spontaneously hypertensive rats (SHR) reportedly have inappropriately high levels of Ang II despite normal plasma renin activity (PRA). Because Ang II stimulates oxidative stress, which in turn quenches nitric oxide, it is possible that Ang II-induced increases in oxidative stress contribute to the increase in blood pressure. Indeed, administering either a converting enzyme inhibitor (to decrease Ang II) or Tempol (a potent antioxidant) reduces blood pressure in SHR. We tested whether decreasing Ang II with a converting enzyme inhibitor reduces oxidative stress as well as MAP in SHR. For this, we divided 12 weeks old SHR into two groups (n=5 each). One group was treated with captopril (100 mg/kg/day added to the drinking water) and the other served as our untreated time controls. After 16 days of treatment, the rats were anesthetised and we measured MAP and collected blood samples to determine PRA, and the plasma levels of Ang II and thiobarbituric acid-reactive substances (TBARS). The captopril-treated rats had a lower MAP than the untreated rats (92±4 vs. 160±5 mmHg, respectively) and an increased PRA (42±1 vs. 26±6 ng/ml/h; captopril-treated vs. untreated rats, respectively). The decreased MAP in the captopril-treated SHR was accompanied by reduced plasma levels of Ang II (630±47 vs. 836±205 pg/ml) and TBARS (5.4±1.0 vs. 3.0±0.2 nmol/ml). Despite the significant decrease in Ang II levels in the captopril-treated SHR, they are still 20-fold higher rhan in normotensive Sprague-Dawley rats (34.0±8.8 pg/ml). In summary, captopril-induced decreases of MAP in SHR are accompanied not only by reduced levels of Ang II, but also by reduced oxidative stress. Because antioxidants also lower MAP in SHR, it suggests that oxidative stress induced by Ang II may play a role in the pathogenesis of the increased blood pressure in SHR.

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Antihypertensive actions of angiotensin-(1-7) in spontaneously hypertensive rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1995.269.1.h313 ◽

1995 ◽

Vol 269 (1) ◽

pp. H313-H319 ◽

Cited By ~ 67

Author(s):

I. F. Benter ◽

C. M. Ferrario ◽

M. Morris ◽

D. I. Diz

Keyword(s):

Blood Pressure ◽

Prostaglandin E2 ◽

Spontaneously Hypertensive Rats ◽

Systolic Pressure ◽

Experimental Hypertension ◽

Electrolyte Balance ◽

Ang Ii ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Plasma Vasopressin

Observations that angiotensin-(1-7) [ANG-(1-7)] may oppose the vasoconstrictor actions of angiotensin II (ANG II) prompted an investigation of the effects of the heptapeptide on the maintenance of elevated blood pressure in spontaneously hypertensive rats (SHR). ANG-(1-7) (24 micrograms.kg-1.h-1) was infused into the jugular vein of 13-wk-old SHR (n = 64), Wistar-Kyoto (WKY, n = 50), and Sprague-Dawley (SD, n = 18) rats for 2 wk, with the use of osmotic minipumps. Blood pressure, fluid and electrolyte balance, plasma vasopressin, and urinary excretion of prostaglandin E2 and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) were measured at days 2, 7, and 12 of the infusion. In SHR, ANG-(1-7) caused a sustained and significant reduction in plasma vasopressin concentration that was associated with an increase in urinary prostaglandin E2 and 6-keto-PGF1 alpha excretion at day 2 after the commencement of the infusion. These changes were accompanied by diuresis and natriuresis during the first 3 days of infusion in SHR but not in WKY or SD rats. Direct measurements of arterial pressure confirmed the lowering effect of ANG-(1-7) on systolic pressure of SHR on day 2 of treatment with a restoration of the pressure by days 7 and 12. These findings, along with our previous demonstration that ANG-(1-7) is an active depressor peptide in the intact animal, suggest that ANG-(1-7) may play a significant role as a vasodepressor system opposing the hemodynamic actions of ANG II in this genetic form of experimental hypertension.

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Antihypertensive Activity of Eucommia Ulmoides Oliv: Male Flower Extract in Spontaneously Hypertensive Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/6432173 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Zhen-Jiang Ding ◽

Chao Liang ◽

Xiao Wang ◽

Xin Yao ◽

Ruo-Han Yang ◽

...

Keyword(s):

Blood Pressure ◽

Aqueous Extract ◽

Spontaneously Hypertensive Rats ◽

Male Flower ◽

Antihypertensive Activity ◽

Eucommia Ulmoides ◽

Ang Ii ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Male Flowers

Eucommia ulmoides Oliv. is a traditional medical plant in Asia; however, it is still unknown whether Eucommia male flowers have an antihypertensive activity. In this study, we found that the aqueous extract of Eucommia ulmoides Oliv. male flowers can lower the blood pressure of SHR in a dose-dependent manner. Mechanistic studies suggested that the aqueous extract of male flowers can promote the mRNA and protein expressions of ACE2 in the kidney of SHR. ELISA assay showed that the plasma levels of ANG II was decreased, while ANG-(1–7) was increased in SHR treated with the aqueous extract of male flowers. ACE2 inhibitor DX600 can reverse the aqueous extract of Eucommia ulmoides Oliv. male flower-induced downregulation of Ang II and upregulation of Ang-(1–7), as well as the reduction of blood pressure in SHR. Moreover, Ang-(1–7)-Mas receptor antagonist A-779 abolished the antihypertensive effects of the aqueous extract of Eucommia ulmoides Oliv. male flower in SHR. The aqueous extract of Eucommia ulmoides Oliv. male flowers exhibited an antihypertensive action through the activation of ACE2-Ang-(1–7)-Mas signaling pathways in spontaneously hypertensive rats.

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Expression of smooth muscle MyHC B in blood vessels of hypertrophied heart in experimentally hypertensive rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00578.2002 ◽

2003 ◽

Vol 284 (2) ◽

pp. R607-R610 ◽

Cited By ~ 3

Author(s):

Katharina Wetzel ◽

Ovidiu Baltatu ◽

Benno Nafz ◽

Pontus B. Persson ◽

Hannelore Haase ◽

...

Keyword(s):

Blood Pressure ◽

Smooth Muscle ◽

Adaptive Response ◽

Spontaneously Hypertensive Rats ◽

Expression Patterns ◽

Ang Ii ◽

Hypertensive Rats ◽

Genetic Origin ◽

Spontaneously Hypertensive ◽

Muscle Myosin

We demonstrated recently a significantly lower fraction of cardiac precapillary arterioles that expressed smooth muscle myosin heavy chain (MyHC) B (SMB) in spontaneously hypertensive rats. To clarify whether this reduction of SMB expression is of genetic origin, we investigated SMB expression in cardiac precapillary arterioles of normotensive and experimentally hypertensive rats (one clip, one kidney or ANG II minipump). We observed similar SMB expression patterns in precapillary arterioles of experimentally hypertensive rats compared with normotensive controls. These observations suggest that the downregulation of SMB in spontaneously hypertensive rats is of genetic origin rather than an adaptive response to chronically enhanced blood pressure and cardiac hypertrophy.

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Soyabean protein hydrolysate prevents the development of hypertension in spontaneously hypertensive rats

British Journal Of Nutrition ◽

10.1079/bjn20041218 ◽

2004 ◽

Vol 92 (3) ◽

pp. 507-512 ◽

Cited By ~ 44

Author(s):

Hsin-Yi Yang ◽

Suh-Ching Yang ◽

Jiun-Rong Chen ◽

Ya-Hui Tzeng ◽

Bor-Cheng Han

Keyword(s):

Blood Pressure ◽

Spontaneously Hypertensive Rats ◽

Plasma Lipids ◽

Protein Hydrolysate ◽

Ace Inhibition ◽

Inhibitory Effect ◽

Left Ventricular ◽

Hypertensive Rats ◽

Spontaneously Hypertensive

The aim of the present study was to investigate the anti-hypertensive and angiotensin-converting enzyme (ACE) inhibition effects of soyabean protein hydrolysate in spontaneously hypertensive rats (SHR). Soyabean protein hydrolysate was prepared by peptic hydrolysis and was added into the feed of SHR (0 % for the S0 group, 0·5 % for the S1 group, and 1 % for the S2 group) for 12 weeks. Systolic blood pressure and mean blood pressure of the S1 (164·3 (sem 4·7); 128·0 (sem 5·0) mmHg) and S2 (156·8 (sem 1·6); 120·8 (sem 3·4) mmHg) groups were significantly lower than those of the S0 group (199·4 (sem 5·2); 158·3 (sem 7·0) mmHg) at the end of the study. In the analysis of ACE activity, plasma and heart ACE activities of the S1 and S2 groups were significantly lower than those of the S0 group, and there were no significant differences in aorta, kidney, and lung ACE activities among all SHR. Soyabean protein hydrolysate had no significant effect on plasma lipids, electrolytes, or on left ventricular wall or aorta wall thickness. The results suggest that the long-term administration of soyabean protein hydrolysate might retard the development of hypertension in SHR by its inhibitory effect on ACE in vivo.

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Ventrolateral medulla in spontaneously hypertensive rats: role of angiotensin II

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1993.264.2.r388 ◽

1993 ◽

Vol 264 (2) ◽

pp. R388-R395 ◽

Cited By ~ 23

Author(s):

H. Muratani ◽

C. M. Ferrario ◽

D. B. Averill

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Spontaneously Hypertensive Rats ◽

Pressor Response ◽

Ventrolateral Medulla ◽

Ang Ii ◽

Gamma Aminobutyric Acid ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Wky Rats

We investigated whether angiotensin II (ANG II), endogenous to the ventrolateral medulla (VLM), contributes to cardiovascular regulation in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. The action of ANG II endogenous to the VLM was examined by microinjection of 100 pmol of [Sar1,Thr8]ANG II into either the rostral (R) or caudal (C) VLM. This ANG II antagonist caused depressor and bradycardic responses in the RVLM and pressor and tachycardic responses in the CVLM. The magnitude of the blood pressure responses was significantly greater (P < 0.01 in RVLM and P < 0.05 in CVLM) in SHRs (-27 +/- 3 mmHg in RVLM and 29 +/- 4 mmHg in CVLM) than in WKY rats (-17 +/- 1 and 17 +/- 2 mmHg, respectively). Suppression of tonic activity of RVLM neurons by bilateral injection of muscimol in the RVLM showed that the pressor response produced by ANG II antagonist injection in the CVLM required the integrity of rostral pressor neurons. The present data suggest that ANG II endogenous to RVLM and CVLM acts as a tonic excitatory agent on vasomotor neurons of the VLM. The contribution of ANG II in the RVLM and CVLM to the prevailing level of blood pressure was significantly (P < 0.01) larger in SHRs vs. WKY rats when the effect of ANG II blockade was measured as the change in blood pressure. Blockade of gamma-aminobutyric acid (GABA)A receptors in the RVLM showed that inhibitory GABAergic input to the RVLM was not diminished in this strain.(ABSTRACT TRUNCATED AT 250 WORDS)

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Hypotensive and Angiotensin-Converting Enzyme Inhibitory Activities ofEisenia fetidaExtract in Spontaneously Hypertensive Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/349721 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Shumei Mao ◽

Chengde Li

Keyword(s):

Blood Pressure ◽

Inhibitory Activity ◽

Spontaneously Hypertensive Rats ◽

Ang Ii ◽

Shr Rats ◽

Hypertensive Rats ◽

Ace Inhibitory Activity ◽

Spontaneously Hypertensive ◽

Ace Inhibitory

Objectives. This study aimed to investigate the antihypertensive effects of anEisenia fetidaextract (EFE) and its possible mechanisms in spontaneously hypertensive rats (SHR rats).Methods. Sixteen-week-old SHR rats and Wistar-Kyoto rats (WKY rats) were used in this study. Rats were, respectively, given EFE (EFE group), captopril (captopril group), or phosphate-buffered saline (PBS) (normal control group and SHR group) for 4 weeks. ACE inhibitory activity of EFEin vitrowas determined. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured using a Rat Tail-Cuff Blood Pressure System. Levels of angiotensin II (Ang II), aldosterone (Ald), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1α) in plasma were determined by radioimmunoassay, and serum nitric oxide (NO) concentration was measured by Griess reagent systems.Results. EFE had marked ACE inhibitory activityin vitro(IC50= 2.5 mg/mL). After the 4-week drug management, SHR rats in EFE group and in captopril group had lower SBP and DBP, lower levels of Ang II and Ald, and higher levels of 6-keto-PGF1αand NO than the SHR rats in SHR group.Conclusion. These results indicate that EFE has hypotensive effects in SHR rats and its effects might be associated with its ACE inhibitory activity.

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Sex and sex hormones influence the development of albuminuria and renal macrophage infiltration in spontaneously hypertensive rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00429.2007 ◽

2007 ◽

Vol 293 (4) ◽

pp. R1573-R1579 ◽

Cited By ~ 66

Author(s):

Jennifer C. Sullivan ◽

Laura Semprun-Prieto ◽

Erika I. Boesen ◽

David M. Pollock ◽

Jennifer S. Pollock

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Sex Hormones ◽

Spontaneously Hypertensive Rats ◽

Macrophage Infiltration ◽

Ang Ii ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Blood Pressures ◽

Over Time

There is a sex difference in hypertensive renal injury, with men experiencing greater severity and a more rapid progression of renal disease than women; however, the molecular mechanisms protecting against renal injury in women are unknown. The goal of this study was to determine whether sex hormones modulate blood pressure and the progression of albuminuria during the developmental phase of hypertension in male and female spontaneously hypertensive rats (SHR). Studies were also performed to examine how sex and sex hormones influence two major risk factors for albuminuria, overactivation of the renin-angiotensin system and oxidative stress. Blood pressure was measured by telemetry in gonad-intact and gonadectomized male and female SHR. Microalbumin excretion, measured over time, and macrophage infiltration were used to assess renal health. Male SHR had significantly higher blood pressures than female SHR, and gonadectomy decreased blood pressures in males with no effect in females. Male SHR displayed a gonad-sensitive increase in albuminuria over time, and female SHR had a gonad-sensitive suppression in macrophage infiltration. Female SHR had greater plasma ANG II levels and similar levels of renal cortical ANG II vs. levels shown in males but less AT1-receptor protein expression in the renal cortex. Female SHR also had a gonad-sensitive decrease in renal oxidative stress. Therefore, the renal protection afforded to female SHR is associated with lower blood pressure, decreased macrophage infiltration, and decreased levels of oxidative stress.

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