scholarly journals ACE Inhibitory and Antihypertensive Activities of Wine Lees and Relationship among Bioactivity and Phenolic Profile

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 679
Author(s):  
Raúl López-Fernández-Sobrino ◽  
Jorge R. Soliz-Rueda ◽  
Maria Margalef ◽  
Anna Arola-Arnal ◽  
Manuel Suárez ◽  
...  

Wine lees (WL) are by-products generated in the winemaking process. The aim of this study was to investigate the angiotensin-converting enzyme inhibitory (ACEi) activity, and the blood pressure (BP) lowering effect of WL from individual grape varieties. The relationship among their activities and phenolic profiles was also studied. Three WL, from Cabernet, Mazuela, and Garnacha grape varieties, were firstly selected based on their ACEi properties. Their phenolic profiles were fully characterized by UHPLC-ESI-Q-TOF-MS. Then, their potential antihypertensive effects were evaluated in spontaneously hypertensive rats (SHR). BP was recorded before and after their oral administrations (2, 4, 6, 8, 24, and 48 h) at a dose of 5 mL/kg bw. Cabernet WL (CWL) exhibited a potent antihypertensive activity, similar to that obtained with the drug Captopril. This BP-lowering effect was related to the high amount of anthocyanins and flavanols present in these lees. In addition, a potential hypotensive effect of CWL was discarded in normotensive Wistar–Kyoto rats. Finally, the ACEi and antihypertensive activities of CWL coming from a different harvest were confirmed. Our results suggest the potential of CWL for controlling arterial BP, opening the door to commercial use within the wine industry.

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1142
Author(s):  
Raúl López-Fernández-Sobrino ◽  
Jorge R. Soliz-Rueda ◽  
Manuel Suárez ◽  
Miquel Mulero ◽  
Lluís Arola ◽  
...  

The antihypertensive effect of wine lees (WL) has been previously evidenced. In this study, the antihypertensive properties of different doses of WL were evaluated in spontaneously hypertensive rats (SHR). In addition, the blood pressure (BP)-lowering effect of dried (dealcoholized) WL powder (WLPW) and the mechanisms involved in its functionality were investigated. Furthermore, a possible hypotensive effect of WLPW was discarded in Wistar–Kyoto (WKY) rats. The administration of WL at different doses caused a dose-dependent decrease in BP of SHR up to 5.0 mL/kg bw, exhibiting the maximum decrease at 6 h post-administration. WLPW caused a greater drop in BP than WL, showing an antihypertensive effect higher and more prolonged than the drug Captopril. Moreover, the BP-lowering effect of WLPW was specific to the hypertensive state since an undesirable hypotensive effect in normotensive WKY rats was ruled out. Finally, WLPW improved oxidative stress and increased the activity of the antioxidant endogen system of SHR. These results suggest that WLPW could be used as functional ingredient for foods or nutraceuticals to ameliorate hypertension. Nevertheless, further clinical studies are needed to evaluate its long-term antihypertensive efficiency.


1997 ◽  
Vol 38 (4) ◽  
pp. 567-567
Author(s):  
Azharul I. Khan ◽  
Johji Kato ◽  
Kazuo Kitamura ◽  
Kenji Kangawa ◽  
Tanenao Eto

1998 ◽  
Vol 275 (5) ◽  
pp. H1627-H1634 ◽  
Author(s):  
Margaret P. Chandler ◽  
David W. Rodenbaugh ◽  
Stephen E. DiCarlo

We tested the hypothesis that postexercise reductions in arterial pressure and heart rate (HR) are mediated by a lowering of the operating point and a reduction in the gain of the arterial baroreflex. To test this hypothesis, spontaneous changes in arterial pressure and the reflex responses of HR were examined before and after a single bout of mild to moderate dynamic exercise in 19 spontaneously hypertensive rats (SHR, 10 male and 9 female). Eleven SHR subjected to sinoaortic denervation (SAD) (6 male, 5 female) were also studied. All rats were instrumented with an arterial catheter for the measurement of arterial pressure and HR. After exercise, arterial pressure and HR were reduced below preexercise levels. Furthermore, the operating point and spontaneous gain (G) of the arterial baroreflex were reduced. Specifically, after exercise, the spontaneous range of HR (P1, 50%), the pressure at the midpoint of the pressure range (P3, 13%) and the HR at the midpoint of the HR range (H3, 10%), the spontaneous minimum HR (P4, 8%) and maximum HR (10%), and G (76%) were significantly attenuated. SAD significantly attenuated the relationship between arterial pressure and HR by reducing G (males 94%, females 95%). These results demonstrate that acute exercise resulted in a postexercise resetting of the operating point and a reduction in the gain of the arterial baroreflex. Furthermore, these data suggest that postexercise reductions in arterial pressure and HR are mediated by a lowering of the operating point of the arterial baroreflex.


1993 ◽  
Vol 265 (1) ◽  
pp. H39-H46 ◽  
Author(s):  
J. M. Qualy ◽  
T. C. Westfall

The relationship between age and central noradrenergic neuronal activity of the paraventricular hypothalamic nucleus (PVH) was examined in 7- to 10-, 12- to 14-, and 30- to 36-wk-old Sprague-Dawley (SD), Wistar-Kyoto (WKY), and spontaneously hypertensive rats (SHR). As an index of noradrenergic activity, endogenous norepinephrine (NE) overflow was assessed utilizing a miniaturized push-pull cannula assembly in unanesthetized freely moving rats. NE overlow under basal, 56 mM K+ stimulation, and in response to pressor/depressor drugs, were examined in all three strains at all ages. Significant increases in basal and K(+)-stimulated overflow of endogenous NE from the PVH were observed in all ages of SHR compared with normotensive controls with the greatest percent increase occurring during the development of hypertension in SHR. In addition, a reciprocal relationship exists with respect to blood pressure and overflow of NE from the PVH such that increases/decreases in blood pressure elicit decreases/increases in NE overflow in all strains at all ages examined. However, developing hypertensive SHR exhibited attenuated decreases in overflow of NE from the PVH compared with age-matched controls and established hypertensive SHR. These results suggest that noradrenergic pathways of the PVH contribute to the development and maintenance of arterial pressure hemostasis and that enhanced central noradrenergic neuronal activity is greatest during the development of hypertension in SHR.


1985 ◽  
Vol 63 (4) ◽  
pp. 387-391 ◽  
Author(s):  
T. M. Scott ◽  
G. Galway

The relationship between sympathetic innervation and arterial medial development has been examined in normotensive, hypertensive, and diabetic rats. Using the jejunal artery as a model, the number of nerve fibres innervating the artery as determined from fluorescent preparations, and the medial thickness and lumen diameter as measured from resin embedded specimens were correlated from animals prepared in various ways. The rats used were normal Sprague–Dawley (SD), SD with induced hypertension, SD with diabetes induced with streptozotocin, SD sympathectomized with 6-hydroxydopamine, spontaneously hypertensive rats (SHR), SHR treated with capsaicin to prevent hypertension development, Wistar Kyoto rats (WKY), and WKY treated with capsaicin. Examination of the jejunal arteries from these rats at 12 weeks of age following normal development, or 8 weeks of hypertension development, or 8 and 12 weeks of diabetes, showed that increased innervation occurred in the SHR under all conditions, and in the diabetic rats after 8 weeks of diabetes. Medial hypertrophy occurred in the SHR and in the SD hypertensive only. It is concluded that the special relationship which exists between the sympathetic innervation and arterial media in the SHR does not occur during hypertension development in the SD rat, nor is it necessary for normal medial development in the SD rat. The sympathetic innervation does appear to have a trophic influence on vascular smooth muscle of diabetic rats, at least in the early stages of the disease.


2010 ◽  
Vol 299 (4) ◽  
pp. F872-F881 ◽  
Author(s):  
Renato O. Crajoinas ◽  
Lucília M. A. Lessa ◽  
Luciene R. Carraro-Lacroix ◽  
Ana Paula C. Davel ◽  
Bruna P. M. Pacheco ◽  
...  

Abnormalities in renal proximal tubular (PT) sodium transport play an important role in the pathophysiology of essential hypertension. The Na+/H+ exchanger isoform 3 (NHE3) represents the major route for sodium entry across the apical membrane of renal PT cells. We therefore aimed to assess in vivo NHE3 transport activity and to define the molecular mechanisms underlying NHE3 regulation before and after development of hypertension in the spontaneously hypertensive rat (SHR). NHE3 function was measured as the rate of bicarbonate reabsorption by means of in vivo stationary microperfusion in PT from young prehypertensive SHR (Y-SHR; 5-wk-old), adult SHR (A-SHR; 14-wk-old), and age-matched Wistar Kyoto (WKY) rats. We found that NHE3-mediated PT bicarbonate reabsorption was reduced with age in the SHR (1.08 ± 0.10 vs. 0.41 ± 0.04 nmol/cm2×s), while it was increased in the transition from youth to adulthood in the WKY rat (0.59 ± 0.05 vs. 1.26 ± 0.11 nmol/cm2×s). Higher NHE3 activity in the Y-SHR compared with A-SHR was associated with a predominant microvilli confinement and a lower ratio of phosphorylated NHE3 at serine-552 to total NHE3 (P-NHE3/total). After development of hypertension, P-NHE3/total increased and NHE3 was retracted out of the microvillar microdomain along with the regulator dipeptidyl peptidase IV (DPPIV). Collectively, our data suggest that the PT is playing a role in adapting to the hypertension in the SHR. The molecular mechanisms of this adaptation possibly include an increase of P-NHE3/total and a redistribution of the NHE3-DPPIV complex from the body to the base of the PT microvilli, both predicted to decrease sodium reabsorption.


2004 ◽  
Vol 92 (3) ◽  
pp. 411-417 ◽  
Author(s):  
Kazuhito Hayakawa ◽  
Masayuki Kimura ◽  
Keiko Kasaha ◽  
Keisuke Matsumoto ◽  
Hiroshi Sansawa ◽  
...  

We investigated the blood-pressure-lowering effects of γ-aminobutyric acid (GABA) and a GABA-enriched fermented milk product (FMG) by low-dose oral administration to spontaneously hypertensive (SHR/Izm) and normotensive Wistar–Kyoto (WKY/Izm) rats. FMG was a non-fat fermented milk product produced by lactic acid bacteria, and the GABA contained in FMG was made from the protein of the milk during fermentation. A single oral dose of GABA or FMG (5 ml/kg; 0·5 mg GABA/kg) significantly (P>0·05) decreased the blood pressure of SHR/Izm from 4 to 8 h after administration, but did not increase that of WKY/Izm rats. The hypotensive activity of GABA was dose-dependent from 0·05 to 5·00 mg/kg in SHR/Izm. During the chronic administration of experimental diets to SHR/Izm, a significantly slower increase in blood pressure with respect to the control group was observed at 1 or 2 weeks after the start of feeding with the GABA or FMG diet respectively (P>0·05) and this difference was maintained throughout the period of feeding. The time profile of blood-pressure change due to administration of FMG was similar to that of GABA. FMG did not inhibit angiotensin 1-converting enzyme. Furthermore, an FMG peptide-containing fraction from reverse-phase chromatography lacked a hypotensive effect in SHR/Izm rats. The present results suggest that low-dose oral GABA has a hypotensive effect in SHR/Izm and that the hypotensive effect of FMG is due to GABA.


1998 ◽  
Vol 274 (2) ◽  
pp. R510-R516 ◽  
Author(s):  
Margaret P. Chandler ◽  
Stephen E. Dicarlo

Arterial pressure (AP), heart rate (HR), cardiac sympathetic tonus (ST), and parasympathetic tonus (PT) were determined in spontaneously hypertensive rats (SHR, 8 male and 8 female) and Wistar-Kyoto normotensive rats (WKY, 8 male and 12 female) before and after acute exercise. Before exercise, hypertensive rats (regardless of gender) had an increased ST (+15 beats/min), increased resting HR (+12 beats/min), and decreased PT (−11 beats/min). Similarly, female rats (regardless of strain) also had an increased ST (+15 beats/min), increased resting HR (+39 beats/min), and decreased PT (−14 beats/min). Hypertensive rats had a significant reduction in AP (−17 ± 3 mmHg), ST (−26 beats/min), PT (−7 beats/min), and HR (−14 beats/min) after exercise. In contrast, AP was not reduced in normotensive rats and ST (+18 beats/min) and HR (+42 beats/min) were increased in female normotensive rats after exercise. However, male normotensive rats had a postexercise reduction in ST (−14 beats/min) and HR (−19 beats/min). In summary, AP, ST, and resting HR were higher whereas PT was lower in hypertensive vs. normotensive rats. Furthermore, females had a higher resting HR, intrinsic HR, and ST and lower PT than male rats. These data demonstrate that gender and the resting level of AP influence cardiac autonomic regulation.


Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Rafael M Jeuken ◽  
Luciana V Rossoni

Structural, mechanical and functional adjustments occur in small mesenteric arteries (SMA) of hypertensive models. However, the role of these properties to trigger hypertension is unknown. As expected, the systolic blood pressure was higher in adult (A, 6-month old) male SHR as compared to Wistar-Kyoto rats (WKY) (WKYA: 125±1.1 vs SHRA: 187±3.3 mmHg*); however, it was similar in young (Y, 6-week old) SHR as compared to age-matched WKY (WKYY: 117±1.8 vs SHRY: 120±2.1 mmHg). The 3rd order mesenteric arteries were mounted in a pressure myograph to analyze the structural [lumen diameter (L), cross sectional area (CSA), wall/lumen ratio (W/L)] and mechanical properties [β, representing wall stiffness]. Endothelium-dependent relaxation to acetylcholine (ACh, 10-10-10-5 M) or -independent relaxation to sodium nitroprusside (SNP, 10-9-10-4 M) were evaluated in SMA using wire myography. At the passive condition (Ca2+-free solution) and intraluminal pressure of 160 mmHg, the L was lower in SMA of both SHR (WKYY: 294±12.0 vs SHRY: 241±4.3*; WKYA: 353±4.7 vs SHRA: 283±6.2 μm*); while the W/L ratio was higher in SHR as compared to age-matched WKY. CSA was similar between age-matched groups. β value was higher in SHR independently of age (WKYY: 5.8±0.4 vs. SHRY: 7.8±0.4*; WKYA: 4.7±0.1 vs SHRA: 6.7±0.4*). The collagen area evaluated by picrosirius red staining was higher in SMA of SHRA as compared to WKYA (WKYA: 15±2.4 vs SHRA: 26±1.8%*), but it did not change in young rats. ACh-induced maximal relaxation was similar in SMA from young groups (WKYY: 93±3.8 vs SHRY: 92±3.1%); however, in SHRA ACh elicited a biphasic curve inducing contraction at concentrations higher than 10-7M, which was not observed in WKYA. Relaxation to SNP did not change among groups. Reactive oxygen species analyzed by dihydroethidium was higher in SMA of SHRA as compared to WKYA (WKYA: 100±3.7 vs SHRA: 126±10.3% of integrated density*), but did not change in young SMA. Although SMA of SHRY present eutrophic inward remodeling and wall stiffening, it does not present collagen deposition, oxidative stress or endothelial dysfunction as observed in SHRA; suggesting that vascular remodeling and wall stiffness of SMA are not sufficient to trigger hypertension, at least when endothelial function is preserved.


2010 ◽  
Vol 298 (6) ◽  
pp. H1769-H1775 ◽  
Author(s):  
YiLin Ren ◽  
Martin A. D'Ambrosio ◽  
Ruisheng Liu ◽  
Patrick J. Pagano ◽  
Jeffrey L. Garvin ◽  
...  

Spontaneously hypertensive rats (SHRs) have normal glomerular capillary pressure even though renal perfusion pressure is higher, suggesting that preglomerular vessels exhibit abnormally high resistance. This may be due to increased superoxide (O2−) production, which contributes to the vasoconstriction in hypertension. We tested the hypothesis that the myogenic response of the afferent arteriole (Af-Art) is exaggerated in SHRs because of increased levels of reactive oxygen species (ROS). Single Af-Arts were microdissected from kidneys of SHRs and Wistar-Kyoto (WKY) rats and microperfused in vitro. When perfusion pressure in the Af-Art was increased stepwise from 60 to 140 mmHg, the luminal diameter decreased by 8.4 ± 2.9% in WKY Af-Arts but fell by 29.3 ± 5.6% in SHR Af-Arts. To test whether ROS production is enhanced during myogenic response in SHRs, we measured chloromethyl-dichlorodihydrofluorescein diacetate acetyl ester (CM-H2DCFDA) florescence before and after increasing intraluminal pressure from 60 to 140 mmHg. Pressure-induced increases in ROS were fourfold greater in SHR Af-Arts compared with WKY Af-Arts (SHR, 48.0 ± 2.2%; and WKY, 12.2 ± 0.3%). To test whether O2− contributes to the myogenic response in SHRs, either the membrane-permeant O2− scavenger Tempol or the nox2-based NADPH oxidase (NOX2) inhibitor gp91 ds-tat were added to the Af-Art lumen and bath and the myogenic response was tested before and after treatment. Both Tempol (10−4 M) and gp91 ds-tat (10−5 M) significantly attenuated the pressure-induced constriction in SHR Af-Arts but not in WKY Af-Arts. We conclude that 1) pressure-induced constriction is exaggerated in SHR Af-Arts, 2) NOX2-derived O2− may contribute to the enhanced myogenic response, and 3) O2− exerts little influence on the myogenic response under normotensive conditions.


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