Abstract MP38: Identification Of A Gut Microbe That Attenuates The Blood Pressure Lowering Effect Of ACEi Quinapril

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Tao Yang ◽  
Xue Mei ◽  
Ethel Tackie-Yarboi ◽  
Jun Kyoung ◽  
Blair Mell ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Drug Resistance ◽  
Drug Metabolism ◽  
Gut Microbiota ◽  
Esterase Activity ◽  
Enzyme Inhibitor ◽  
Fecal Microbiota ◽  
Blood Pressure Lowering Effect ◽  
Spontaneously Hypertensive ◽  
Cecal Microbiota

Introduction: Treatment resistant hypertension (rHTN) is present in ~20% of all hypertensive patients. rHTN is critical in African American patients who experience early onset, severe outcomes, and weak responsiveness to angiotensin converting enzyme inhibitor (ACEi). The mechanism for drug resistance is unknown. Gut microbiota harbors biotransformative enzymes such as esterase, which may hydrolyze ACEis, reducing absorption. Our study was to identify microbe responsible for ACEi resistance. Methods: 16-week-old male Spontaneously Hypertensive Rats (SHR) were gavaged with (N=12) or without (N=6) Vancomycin, Meropenem, and Omeprazole (VMO) 50 mg/kg/day for five days to deplete the gut microbiota. A single 8mg/kg dose of quinapril was given to SHR and SHR+VMO before blood pressure (BP) recording via telemetry. Quinapril catabolism was quantified by liquid chromatography-mass spectrometry. Bacterial esterase activity was monitored by hydrolysis of p-nitro-phenylbutyrate. Cecal microbiota was analyzed by 16S rDNA. Fecal microbiota were analyzed by metagenomics in 29 (16 black, 13 white) HTN patients. Results: Quinapril lowered BP more in the SHR+VMO than SHR ( P <0.0001). With a 50% reduction in bacterial 16S copy numbers ( P <0.0001), the SHR+VMO group showed (1) reduced Coprococcus ( P <0.0001); (2) lower esterase activity per gram of cecal microbiota to hydrolyze quinapril ( P =0.0065); (3) a 50% lower reduction in quinapril quantity (nmol) after incubation with 1mg of cecal lysate for 3 hr ( P <0.0001); (4) decreased bacterial genes in KEGG drug metabolism pathway ( P <0.0001). The abundance of Coprococcus positively correlated with genes in drug metabolism ( P <0.0001). Importantly, co-administration of quinapril with C. comes, a species in Coprococcus genus, reduced the BP-lowering effects of quinapril in the SHR ( P <0.0001). Comparison of human microbiota demonstrated a higher abundance of C. comes in the black hypertensives (poor ACEi responder) than the white (ACEi responder) ( P =0.0167). Conclusion: We, for the first time, demonstrate a previously unrecognized role of gut microbes in reducing ACEi effectiveness. This serves a foundation for expanding clinical management of antihypertensive drug resistance via manipulation of gut microbiota.

scholarly journals Blood Pressure-Lowering Effect of Wine Lees Phenolic Compounds Is Mediated by Endothelial-Derived Factors: Role of Sirtuin 1

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1073
Author(s):  
Raúl López-Fernández-Sobrino ◽  
Jorge R. Soliz-Rueda ◽  
Javier Ávila-Román ◽  
Anna Arola-Arnal ◽  
Manuel Suárez ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Antihypertensive Effect ◽  
Sirtuin 1 ◽  
Dependent Manner ◽  
Blood Pressure Lowering Effect ◽  
Synthesis Inhibitor ◽  
Spontaneously Hypertensive ◽  
Lowering Effect ◽  
Pressure Lowering ◽  
Endothelial Gene Expression

The antihypertensive effect of wine lees powder (WLPW) from a Cabernet grape variety was related to its high content in flavanols and anthocyanins compounds. This study investigates the involvement of endothelial-derived factors and SIRT1 in its bioactivity. Spontaneously hypertensive rats (SHR) were orally administered water or WLPW (125 mg/kg bw). Posteriorly, both groups were intraperitoneally administered saline, Nω-nitro-L-arginine methyl ester (L-NAME), a nitric oxide (NO) synthesis inhibitor, indomethacin, a prostacyclin synthesis inhibitor, or sirtinol, an inhibitor of sirtuins. Blood pressure (BP) was recorded before and 6 h after WLPW administration. In an additional experiment, SHR were administered water or WLPW and endothelial expressions of eNos, Sirt1, Nox4, and Et1 were determined. The BP-lowering properties of WLPW were abolished by L-NAME and partially reduced by indomethacin, demonstrating that WLPW antihypertensive effect was mediated by changes in NO availability, although prostacyclin also contributed to this activity. Moreover, BP-lowering effect was reduced by sirtinol, indicating that WLPW decreased BP in a SIRT1-dependent manner. Furthermore, WLPW upregulated eNos and Sirt1 and downregulated Nox4 and Et1 endothelial gene expression. These results evidence the vasoprotective effect of WLPW and show that its antihypertensive effect in SHR is endothelium dependent and mediated by SIRT1.

scholarly journals Alterations in the gut microbiota can elicit hypertension in rats

2017 ◽  
Vol 49 (2) ◽  
pp. 96-104 ◽  
Author(s):  
Sareema Adnan ◽  
James W. Nelson ◽  
Nadim J. Ajami ◽  
Venugopal R. Venna ◽  
Joseph F. Petrosino ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Gut Microbiota ◽  
Systolic Blood Pressure ◽  
Ribosomal Rna ◽  
Shr Rats ◽  
Spontaneously Hypertensive ◽  
Gut Dysbiosis ◽  
16S Ribosomal Rna Gene ◽  
Previously Treated ◽  
Normotensive Strain

Gut dysbiosis has been linked to cardiovascular diseases including hypertension. We tested the hypothesis that hypertension could be induced in a normotensive strain of rats or attenuated in a hypertensive strain of rats by exchanging the gut microbiota between the two strains. Cecal contents from spontaneously hypertensive stroke prone rats (SHRSP) were pooled. Similarly, cecal contents from normotensive WKY rats were pooled. Four-week-old recipient WKY and SHR rats, previously treated with antibiotics to reduce the native microbiota, were gavaged with WKY or SHRSP microbiota, resulting in four groups; WKY with WKY microbiota (WKY g-WKY), WKY with SHRSP microbiota (WKY g-SHRSP), SHR with SHRSP microbiota (SHR g-SHRSP), and SHR with WKY microbiota (SHR g-WKY). Systolic blood pressure (SBP) was measured weekly using tail-cuff plethysmography. At 11.5 wk of age systolic blood pressure increased 26 mmHg in WKY g-SHRSP compared with that in WKY g-WKY (182 ± 8 vs. 156 ± 8 mmHg, P = 0.02). Although the SBP in SHR g-WKY tended to decrease compared with SHR g-SHRSP, the differences were not statistically significant. Fecal pellets were collected at 11.5 wk of age for identification of the microbiota by sequencing the 16S ribosomal RNA gene. We observed a significant increase in the Firmicutes:Bacteroidetes ratio in the hypertensive WKY g-SHRSP, as compared with the normotensive WKY g-WKY ( P = 0.042). Relative abundance of multiple taxa correlated with SBP. We conclude that gut dysbiosis can directly affect SBP. Manipulation of the gut microbiota may represent an innovative treatment for hypertension.

Dietary calcium modulates renal BBM angiotensin II binding and Na(+)-H+ antiporter activity in SHR

1991 ◽  
Vol 260 (5) ◽  
pp. F657-F662
Author(s):  
M. Levi ◽  
W. L. Henrich
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Brush Border Membrane ◽  
Spontaneously Hypertensive Rat ◽  
Ang Ii ◽  
Blood Pressure Lowering Effect ◽  
Spontaneously Hypertensive ◽  
Pressure Lowering ◽  
Number Of Binding Sites ◽  
Dissociation Constant Kd

Dietary Ca is an important modulator of blood pressure in the spontaneously hypertensive rat (SHR). Since the kidney plays a key role in the pathogenesis of hypertension, the purpose of this study was to determine the potential renal mechanisms of the blood pressure-lowering effect of increasing dietary Ca content. In 21-day-old SHR fed 0.1 vs. 3.6% Ca diet for 14 days, increasing dietary Ca had no significant effects on basal [704 +/- 50 in 0.1% Ca vs. 784 +/- 61 ng angiotensin I (ANG I).mg-1.h-1 in 3.6% Ca, P = not significant (NS)], isoproterenol-stimulated (1,057 +/- 52 in 0.1% Ca vs. 1,104 +/- 59 ng ANG I.mg-1.h-1 in 3.6% Ca, P = NS), or angiotensin II (ANG II)-inhibited (370 +/- 50 in 0.1% Ca vs. 411 +/- 39 ng ANG I.mg-1.h-1 in 3.6% Ca, P = NS) renal superficial cortical slice renin release. In contrast, in apical brush-border membrane (BBM) vesicles isolated from the superficial cortex, increasing dietary Ca caused a significant decrease in ANG II binding, which was mediated by a decrease in the number of binding sites (Bmax, 376 +/- 14 in 0.1% Ca vs. 234 +/- 6 fmol ANG II/mg BBM protein in 3.6% Ca, P less than 0.01), and no change in the affinity [dissociation constant (Kd), 17.8 +/- 1.4 in 0.1% Ca vs. 13.4 +/- 2.8 nM ANG II in 3.6% Ca, P = NS].(ABSTRACT TRUNCATED AT 250 WORDS)

Partial Replacement of Sodium by Potassium in the Diet Restores Impaired Noradrenaline Inactivation and Lowers Blood Pressure in Stroke-Prone Spontaneously Hypertensive Rats

1981 ◽  
Vol 61 (s7) ◽  
pp. 69s-71s ◽  
Author(s):  
R. Dietz ◽  
A. Schömig ◽  
W. Rascher ◽  
R. Strasser ◽  
U. Ganten ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Dietary Intake ◽  
Spontaneously Hypertensive Rats ◽  
Partial Replacement ◽  
Hypertensive Rats ◽  
Blood Pressure Lowering Effect ◽  
Spontaneously Hypertensive ◽  
Pressure Lowering ◽  
Metabolism Of Noradrenaline ◽  
Inactivation Of Noradrenaline

1. Partial replacement of sodium by potassium in the diet attenuates the rise in blood pressure in stroke-prone spontaneously hypertensive rats (SHR-SP). 2. The blood pressure-lowering effect of potassium cannot be ascribed to a reduction in intravascular volume. 3. The increased dietary intake of potassium leads to a reduced stimulation of the sympathoneuronal and sympathoadrenal system by cold compared with the response of sodium-loaded rats. 4. The impaired inactivation of noradrenaline observed in sodium-loaded SHR-SP is improved in SHR-SP on a potassium-substituted diet. 5. It is concluded that changes in dietary intake of sodium and potassium modulate sympathetic activity and the metabolism of noradrenaline, both of which are related to the development of hypertension in SHR-SP.

scholarly journals Circadian disruption and divergent microbiota acquisition under extended photoperiod regimens in chicken

2018 ◽  
Author(s):  
Anne-Sophie Charlotte Hieke ◽  
Shawna Marie Hubert ◽  
Giridhar Athrey
Keyword(s):  
Gut Microbiota ◽  
Early Life ◽  
Clock Genes ◽  
Later Life ◽  
Fecal Microbiota ◽  
Circadian Disruption ◽  
Management Tool ◽  
Light Regimes ◽  
Cecal Microbiota ◽  
Microbiota Structure

The gut microbiota is crucial for metabolic homeostasis, immunity, growth and overall health, and it recognized that early-life microbiota acquisition is a pivotal event for later life health. Recent studies show that gut microbiota diversity and functional activity are synchronized with the host circadian rhythms in healthy individuals, and circadian disruption elicits dysbiosis in mammalian models. However, no studies have determined the associations between circadian disruption in early life, microbiota colonization, and the consequences for microbiota structure in birds. Chickens, as a major source of protein around the world, are one of the most important agricultural species, and their gut and metabolic health are significant concerns. The poultry industry routinely employs extended photoperiods (>18 hours’ light) as a management tool, and their impacts on the chicken circadian, its role in gut microbiota acquisition in early life, and consequences for later life microbiota structure remain unknown. In this study, the objectives were to a) characterize chicken circadian activity under two different light regimes (12/12 hours’ Light/Dark and 23/1 hours Light/Dark), b) characterize gut microbiota acquisition and composition in the first four weeks of life, c) determine if gut microbiota oscillate in synchrony with the host circadian, and d) to determine if fecal microbiota is representative of cecal microbiota. Expression of clock genes (clock, bmal1, and per2) were assayed, and fecal and cecal microbiota was characterized using 16s rRNA amplicon analyses from birds raised under two photoperiod treatments. Chickens raised under 12/12 LD photoperiods exhibited rhythmic clock gene activity, which was absent in birds raised under the extended (23/1 LD) photoperiod. This study is also the first to report differential microbiota acquisition under different photoperiod regimes. Gut microbiota members showed a similar oscillating pattern as the host, but this association was not as strong as found in mammals. Finally, the fecal microbiota was found to be not representative of cecal microbiota membership and structure. This is one of the first studies to demonstrate the use of photoperiods to modulate microbiota acquisition, and show its potential utility as a tool to promote the colonization of beneficial microorganisms.

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