scholarly journals Tandem mass spectrum similarity-based network analysis using 13C-labeled and non-labeled metabolome data to identify the biosynthesis pathway of the blood pressure-lowering asparagus metabolite asparaptine A

2021 ◽  
Author(s):  
Ryo Nakabayashi ◽  
Yutaka Yamada ◽  
Tomoko Nishizawa ◽  
Tetsuya Mori ◽  
Takashi Asano ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Network Analysis ◽  
Biosynthetic Pathway ◽  
Oral Feeding ◽  
Asparagus Officinalis ◽  
Tandem Mass ◽  
Naturally Occurring ◽  
Pressure Lowering ◽  
Mouse Species

AbstractAsparaptine, a conjugate of arginine and asparagusic acid, was found in asparagus (Asparagus officinalis) as a naturally occurring inhibitor of angiotensin-converting enzyme (ACE) in vitro. The biosynthetic pathway to asparaptine is largely unknown; however, it is suggested that asparagusic acid may be biosynthesized from valine. To determine which metabolites are involved in the asparaptine biosynthetic pathway, we performed tandem mass spectrometry similarity-based metabolome network analysis using 13C labeled and non-labeled valine-fed asparagus calluses. We determined that valine is used as a starting material, S(2-carboxy-n-propyl)-cysteine as an intermediate, and two new metabolites as asparaptine analogs, lysine- and histidine-type conjugates, are involved in the pathway. Asparaptine was therefore renamed asparaptine A (arginine type), and the two analogs were named asparaptines B (lysine type) and C (histidine type). Oral feeding of asparaptine A to a hypertensive mouse species showed that this metabolite lowers both blood pressure and heart rate within two hours and both of which were back to normal two days later. These results suggest that asparaptine A may not only have effects as an ACE inhibitor, but also has β-antagonistic effects, which are well-known to be preventive for cardiovascular diseases.

Blood Pressure-Lowering Effects of Alacalase-Hydrolyzed Camellia Seed Hull In Vitro and in Spontaneous Hypertensive Rats

2017 ◽  
Vol 20 (7) ◽  
pp. 720-723 ◽  
Author(s):  
Ho-Jeong Lim ◽  
Mi-So Kim ◽  
Da-Som Kim ◽  
Young Jun Kim ◽  
Jin Hyup Lee ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Lowering ◽  
Hypertensive Rats ◽  
Pressure Lowering ◽  
Seed Hull

scholarly journals New bradykinin analogues acylated on the N-terminus: effect on rat uterus and blood pressure.

2007 ◽  
Vol 54 (1) ◽  
pp. 193-198 ◽  
Author(s):  
Olga Labudda ◽  
Tomasz Wierzba ◽  
Dariusz Sobolewski ◽  
Małgorzata Sleszyńska ◽  
Łukasz Gawiński ◽  
...  
Keyword(s):  
Blood Pressure ◽  
The Other ◽  
Rat Uterus ◽  
Rat Blood ◽  
Other Hand ◽  
N Terminus ◽  
Pressure Lowering ◽  
Bradykinin Analogues ◽  
Group D

Our previous studies suggested that acylation of the N-terminus of several known B2 antagonists with various kinds of bulky acyl groups consistently improved their antagonistic potency in rat blood pressure assay. On the other hand, our earlier observations also seemed to suggest that the effects of acylation on the contractility of isolated rat uterus depended substantially on the chemical character of the acyl group, as we observed that this modification might either change the range of antagonism or even transform it into agonism. Bearing all this in mind, we decided to synthesize seven new analogues of bradykinin by N-terminal acylation with various acyl groups of a moderately potent B2 antagonist, previously synthesized by Stewart's group, D-Arg-Arg-Pro-Hyp-Gly-Thr-Ser-D-Phe-Thi-Arg. The analogues were tested in vitro for their blood pressure-lowering and uterotonic activities. The modifications either preserved or increased the antagonistic potency in the rat blood pressure test. On the other hand, all seven substituents negatively influenced the interaction with the rat uterine receptors. Our results may be helpful for designing new B2 agonists and antagonists.

scholarly journals Consumption of Cuban Policosanol Improves Blood Pressure and Lipid Profile via Enhancement of HDL Functionality in Healthy Women Subjects: Randomized, Double-Blinded, and Placebo-Controlled Study

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Kyung-Hyun Cho ◽  
Suk-Jeong Kim ◽  
Dhananjay Yadav ◽  
Jae-Yong Kim ◽  
Jae-Ryong Kim
Keyword(s):  
Blood Pressure ◽  
Cholesterol Efflux ◽  
Blood Pressure Lowering ◽  
Blood Pressure Lowering Effect ◽  
Transfer Protein ◽  
Hdl Functionality ◽  
Pressure Lowering ◽  
Double Blinded

Policosanol has been reported to improve blood pressure, lipid profile, and HDL functionality via inhibition of cholesteryl ester transfer protein (CETP) both in vitro and in vivo in zebrafish and human models. However, there are limited reports and randomized, double-blinded trials on policosanol that could advocate the blood pressure-lowering effect in prehypertensive participants. Therefore, we performed in vitro, in vivo, and ex vivo experiments to provide more substantial and concrete data on the blood pressure-lowering effect of policosanol. Consumption of policosanol for 8 weeks enhanced plasma antioxidant activity. In the policosanol group, plasma total cholesterol (TC) and triglyceride (TG) levels were reduced up to 20% and 14%, respectively, and HDL-C level was elevated up to 1.3-fold compared to that at week 0. TG/HDL-C and cholesteryl ester transfer protein (CETP) activities were reduced up to 36% and 20%, respectively. Uptake of oxidized LDL in macrophages was reduced as oxidized species levels were reduced, and HDL2-associated paraoxonase activities were enhanced by 60% compared to those at week 0. Encapsulation of policosanol into reconstituted HDL (PCO-rHDL) enhanced cholesterol efflux activity and insulin secretion capacity. In conclusion, consumption of policosanol for 8 weeks in healthy female subjects resulted in lowered blood pressure and CETP activity via elevation of HDL/apoA-I contents and enhancement of HDL functionalities, including cholesterol efflux and insulin secretion. These functional enhancements of HDL can contribute to the prevention of aging-related diseases, hypertension, and stroke.

Abstract 298: Cytochrome P4501A1 Contributes to Nitric Oxide-Dependent Vasodilation and Blood Pressure Lowering on an Omega-3 Polyunsaturated Fatty Acid-Enriched Diet

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Larry N Agbor ◽  
Mary T Walsh ◽  
Mary K Walker
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Mesenteric Arteries ◽  
Omega 3 ◽  
Blood Pressure Lowering ◽  
Cytochrome P4501a1 ◽  
Pressure Lowering ◽  
Normal Chow ◽  
Blood Pressure Responses

Cytochrome P4501A1 (CYP1A1) stereospecifically metabolizes omega-3 polyunsaturated fatty acids (n-3 PUFA) to potent vasodilators in vitro. We have previously reported that CYP1A1 knockout (KO) mice are hypertensive and exhibit significantly reduced vasodilatory responses to the n-3 PUFAs, eicosapentaenoic and docosahexaenoic acids. We next tested the hypothesis that CYP1A1 KO mice would exhibit significantly different vascular and blood pressure responses to diets enriched in n-3 versus n-6 PUFAs. CYP1A1 wildtype (WT) and KO mice were fed normal chow or diets enriched in either n-3 or n-6 PUFAs for 2 mo, and then blood pressure was assessed by radiotelemetry ± nitric oxide synthase (NOS) inhibitor (NG-nitro-L-Arginine). Acetylcholine (Ach)-mediated vasodilation was assessed in first order mesenteric arteries, and endothelial NOS and phospho-eNOS were measured in the aorta. We found that an n-3 enriched diet significantly reduced mean arterial pressure (MAP) in CYP1A1 KO mice (Chow: 116.0 ± 1.2; n-3 diet: 107.6 ± 1.5, p<0.05) with no effect in WT mice (Chow: 103.0 ± 0.9; n-3 diet: 105.0 ± 2.5). In contrast, an n-6 enriched diet significantly increased MAP in WT mice (Chow: 103.0 ± 0.9; n-6: 118.2 ± 4.1, p<0.05) with no effect in KO mice (Chow: 116.0 ± 1.2; n-6: 115.3 ± 1.5). Interestingly, NOS inhibition increased blood pressure significantly more in the CYP1A1 WT mice (+16 ± 0.5 mmHg) than KO mice (+11 ± 0.6, p<0.002) on an n-3 diet, but resulted in similar increases in blood pressure in both genotypes on an n-6 diet (WT: +11 ± 1.8; KO: +11 ± 0.8). In addition, CYP1A1 KO mice on an n-3 enriched diet exhibited significantly reduced Ach-dependent dilation in mesenteric arteries and reduced expression of aortic phospho-eNOS, compared to WT. However, neither of these endpoints were altered in KO mice on an n-6 diet, compared to WT. Taken together, these data suggest that CYP1A1 contributes to the NO-mediated vasodilation and blood pressure lowering benefits derived from dietary n-3 PUFAs.

scholarly journals Computational protein design enables a novel one-carbon assimilation pathway

2015 ◽  
Vol 112 (12) ◽  
pp. 3704-3709 ◽  
Author(s):  
Justin B. Siegel ◽  
Amanda Lee Smith ◽  
Sean Poust ◽  
Adam J. Wargacki ◽  
Arren Bar-Even ◽  
...  
Keyword(s):  
Protein Design ◽  
Biosynthetic Pathway ◽  
Carbon Fixation ◽  
Carbon Assimilation ◽  
Dihydroxyacetone Phosphate ◽  
Design Tools ◽  
Chemical Transformations ◽  
Central Metabolism ◽  
Naturally Occurring

We describe a computationally designed enzyme, formolase (FLS), which catalyzes the carboligation of three one-carbon formaldehyde molecules into one three-carbon dihydroxyacetone molecule. The existence of FLS enables the design of a new carbon fixation pathway, the formolase pathway, consisting of a small number of thermodynamically favorable chemical transformations that convert formate into a three-carbon sugar in central metabolism. The formolase pathway is predicted to use carbon more efficiently and with less backward flux than any naturally occurring one-carbon assimilation pathway. When supplemented with enzymes carrying out the other steps in the pathway, FLS converts formate into dihydroxyacetone phosphate and other central metabolites in vitro. These results demonstrate how modern protein engineering and design tools can facilitate the construction of a completely new biosynthetic pathway.

The Involvement of Platelets and the Coronary Vasculature in Collagen-Induced Sudden Death in Rabbits

1985 ◽  
Vol 53 (01) ◽  
pp. 070-074 ◽  
Author(s):  
G Mallarkey ◽  
G M Smith
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Platelet Count ◽  
Sudden Death ◽  
Myocardial Ischaemia ◽  
Plasma Levels ◽  
Sodium Citrate ◽  
Plasma Samples ◽  
Calcium Entry Blockers

SummaryThe mechanism of collagen-induced sudden death in rabbits was studied by measuring blood pressure (BP), heart rate, ECG, the continuous platelet count and the plasma levels of thromboxane B2 (TxB2) and 6-keto prostaglandin Fia (6-keto PGF1α). Death was preceded by myocardial ischaemia and a sharp fall in BP which occurred before any fall in platelet count was observed. The calcium entry blockers (CEBs), verapamil, nifedipine and PY 108-068 protected the rabbits from sudden death without any significant effect on the decrease in the platelet count or increase in plasma TxB2 levels. 6-keto PGF1α could not be detected in any plasma samples. Indomethacin and tri-sodium citrate also protected the rabbits but significantly reduced the fall in platelet count and plasma TxB2. In vitro studies on isolated aortae indicated that verapamil non-specifically inhibited vasoconstriction induced by KC1, adrenaline and U46619 (a thromboxane agonist). It is concluded that CEBs physiologically antagonize the vasoconstricting actions of platelet-derived substances and that it is coronary vasoconstriction that is primarily the cause of death.

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