Increased Ca2+ Buffering Function of Sarcoplasmic Reticulum in Small Mesenteric Arteries from Spontaneously Hypertensive Rats

Nomura, Yukiko; Asano, Masahisa

doi:10.1291/hypres.25.231

Cited by 8 publications

(7 citation statements)

References 40 publications

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“…Increased alpha-adrenergic response in small mesenteric arteries has been involved in increased blood pressure in SHR [43], [44]. As expected, both quercetin and isorhamnetin incubated during 30 min, inhibited the contractile response induced by the alpha-adrenergic receptor agonist phenylephrine.…”

Section: Discussionsupporting

confidence: 72%

Glucuronidated Quercetin Lowers Blood Pressure in Spontaneously Hypertensive Rats via Deconjugation

et al. 2012

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BackgroundChronic oral quercetin reduces blood pressure and restores endothelial dysfunction in hypertensive animals. However, quercetin (aglycone) is usually not present in plasma, because it is rapidly metabolized into conjugated, mostly inactive, metabolites. The aim of the study is to analyze whether deconjugation of these metabolites is involved in the blood pressure lowering effect of quercetin.Methodology/Principal FindingsWe have analyzed the effects on blood pressure and vascular function in vitro of the conjugated metabolites of quercetin (quercetin-3-glucuronide, Q3GA; isorhamnetin-3-glucuronide, I3GA; and quercetin-3′-sulfate, Q3'S) in spontaneously hypertensive rats (SHR). Q3GA and I3GA (1 mg/kg i.v.), but not Q3'S, progressively reduced mean blood pressure (MBP), measured in conscious SHR. The hypotensive effect of Q3GA was abolished in SHR treated with the specific inhibitor of β-glucuronidase, saccharic acid 1,4-lactone (SAL, 10 mg/ml). In mesenteric arteries, unlike quercetin, Q3GA had no inhibitory effect in the contractile response to phenylephrine after 30 min of incubation. However, after 1 hour of incubation Q3GA strongly reduced this contractile response and this effect was prevented by SAL. Oral administration of quercetin (10 mg/Kg) induced a progressive decrease in MBP, which was also suppressed by SAL.ConclusionsConjugated metabolites are involved in the in vivo antihypertensive effect of quercetin, acting as molecules for the plasmatic transport of quercetin to the target tissues. Quercetin released from its glucuronidated metabolites could be responsible for its vasorelaxant and hypotensive effect.

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Section: Discussionsupporting

confidence: 72%

Glucuronidated Quercetin Lowers Blood Pressure in Spontaneously Hypertensive Rats via Deconjugation

et al. 2012

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“…For instance, a large Ca 2ϩ influx and a high basal [Ca 2ϩ ] c have been seen during rest in conduit arteries (i.e., the aorta and carotid and femoral arteries) from SHRs compared with normotensive rats (Jelicks and Gupta, 1990;Asano et al, 1996). This has also been found in small mesenteric arteries from SHRs, where the sarcoplasmic reticulum has a larger capacity for Ca 2ϩ storage (Nomura and Asano, 2002). Donohue et al (1988) found an enhanced norepinephrine release from different tissues with rich sympathetic innervation in SHRs, with respect to normotensive rats.…”

Section: Discussionmentioning

confidence: 92%

“…Alterations of intracellular Ca 2ϩ homeostatic mechanisms could also account for the differences. In fact, a large Ca 2ϩ influx and a high cytosolic Ca 2ϩ concentration ([Ca 2ϩ ] c ) has been seen even during rest in conduit arteries i.e., aorta, carotid, and femoral arteries from SHRs compared with normotensive rats (Jelicks and Gupta, 1990;Asano et al, 1996); this also has been found in small mesenteric arteries from SHRs, where the sarcoplasmic reticulum has a larger capacity for Ca 2ϩ storage (Nomura and Asano, 2002).…”

mentioning

confidence: 99%

Role of the Endoplasmic Reticulum and Mitochondria on Quantal Catecholamine Release from Chromaffin Cells of Control and Hypertensive Rats

Miranda-Ferreira

Pascual²,

Caricati‐Neto³

et al. 2009

J Pharmacol Exp Ther

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Here, we present the first study on the effects of compounds that interfere with calcium (Ca 2ϩ ) handling by the endoplasmic reticulum (ER) and mitochondria on amperometrically measured quantal catecholamine release from single adrenal chromaffin cells of control and spontaneously hypertensive rats (SHRs). Acetylcholine (ACh) or K ϩ pulses triggered spike bursts of secretion by Ca 2ϩ entry through Ca 2ϩ channels. ER Ca 2ϩ release triggered by a mixture of caffeine, ryanodine, and thapsigargin (CRT) or carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) (a mitochondrial protonophore) also caused bursts of secretory spikes. The spike bursts generated by ACh, K ϩ , CRT, and FCCP were 3 to 4 times longer in SHRs compared with control cells; furthermore, the individual spikes were faster and had 3-fold greater quantal size. In additional experiments, a 90-s treatment was made with CRT or FCCP to block Ca 2ϩ handling by the ER and mitochondria. In these conditions, the integrated spike burst responses elicited by ACh and K ϩ were potentiated 2-to 3-fold in control and SHR cells. This suggests that variations in Ca 2ϩ entry and its subsequent redistribution into the ER and mitochondria are not responsible for the greater secretion seen in SHRs compared with control cells; rather, such differences seem to be due to greater quantal content of spike bursts and to greater quantal size of individual amperometric events.The differential release into the circulation of the catecholamines norepinephrine and epinephrine from the adrenal medullary gland, either in basal or stressful conditions, is tightly regulated by various central (Folkow and Von Euler, 1954) and peripheral splanchnic nerve stimulation (Mirkin, 1961;Klevans and Gebber, 1970) patterns. Alteration of the activity of the sympathoadrenal medullary axis and of the rate of catecholamine release has been implicated in the pathogenesis of essential hypertension, as proven by three facts: 1) the classic effects of drugs interfering with this axis, used to treat hypertensive patients such as blockers of ␣-and ␤-adrenergic receptors, reserpine, ␣-methyldopa, ganglionic blocking agents, guanethidine, or angiotensin II receptor blockers (Westfall and Westfall, 2007); 2) plasma levels of norepinephrine and epinephrine are augmented in spontaneously hypertensive rats (SHRs) (Iriuchijima, 1973;Grobecker et al., 1975;Pak, 1981), as happens to be the case in humans suffering essential hypertension (Goldstein, 1983); and 3) hypertensive patients have elevated sympathetic nerve activity, as revealed with microneurography (Anderson et al., 1989).Numerous studies support the notion that pre-and postsynaptic sympathetic dysfunctions are involved in the pathophysiology of human or animal primary hypertension (Tsuda and Masuyama, 1991;de Champlain et al., 1999). Studies on presynaptic mechanisms have been performed in SHRs, showing that norepinephrine release is increased in different tissues rich in sympathetic nerve endings (Donohue

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“…After decapitation, the superior mesenteric vascular bed was dissected away from the intestines and placed in a Krebs solution of the following composition (in mmol/l): NaCl 115.0, KCl 4.7, CaCl2 2.5, MgCl2 1.2, NaHCO3 25.0, KH2PO4 1.2 and dextrose 10.0. As a small artery, the second to third branches (150-250 µm outside diameter) of the superior mesenteric artery were isolated and cut into helical strips (0.4-0.6 mm in width, 5-6 mm in length) (9)(10)(11). As a large artery, the middle part (0.7-0.9 mm outside diameter) of the superior mesenteric artery was cut into helical strips (0.7-0.8 7-8 mm) (9,11).…”

Section: Preparation Of Arterial Stripsmentioning

confidence: 99%

Comparison of Inhibitory Effects of Y-27632, a Rho Kinase Inhibitor, in Strips of Small and Large Mesenteric Arteries from Spontaneously Hypertensive and Normotensive Wistar-Kyoto Rats.

Asano

Nomura

2003

Hypertens Res

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Since Y-27632, a specific inhibitor of Rho kinase, decreases the blood pressure in spontaneously hypertensive rats (SHR), it is suggested that Rho kinase is involved in the pathophysiology of hypertension. However, the effects of Y-27632 on isolated resistance arteries have never been determined. This study aimed to examine the possible role of the Rho/Rho kinase pathway during arterial contraction in isolated resistance arteries from SHR. The profile of arterial relaxant effects of Y-27632 was compared in endothelium-denuded strips of small and large mesenteric arteries from 13-week-old SHR and normotensive Wistar-Kyoto rats (WKY). The addition of 10(-6) mol/l norepinephrine (NE) to the strips of small arteries caused an initial peak followed by a tonic contraction in both strains. There was no difference between the two strains in either the initial peak or the tonic contraction. The addition of Y-27632 (0.3-3 micromol/l) to the tonic contraction of these strips caused a concentration-dependent relaxation in both strains. The relaxation was greater in SHR than in WKY. Similar results were observed in strips of large arteries. The relaxant effects of Y-27632 were greater in the large artery than in the small artery. Y-27632 also induced a concentration-dependent relaxation in strips precontracted with 65.9 mmol/l K+ depolarization. In both arteries, this relaxation was greater in SHR. The relaxant effects of Y-27632 were greater in the K+-contracted strips than in the NE-contracted strips. We conclude that Y-27632 shows the greater relaxant effects on the SHR arteries, and the effects are more evident in the large artery and in the K+-contracted strips.

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Increased Ca2+ Buffering Function of Sarcoplasmic Reticulum in Small Mesenteric Arteries from Spontaneously Hypertensive Rats

Cited by 8 publications

References 40 publications

Glucuronidated Quercetin Lowers Blood Pressure in Spontaneously Hypertensive Rats via Deconjugation

Glucuronidated Quercetin Lowers Blood Pressure in Spontaneously Hypertensive Rats via Deconjugation

Role of the Endoplasmic Reticulum and Mitochondria on Quantal Catecholamine Release from Chromaffin Cells of Control and Hypertensive Rats

Comparison of Inhibitory Effects of Y-27632, a Rho Kinase Inhibitor, in Strips of Small and Large Mesenteric Arteries from Spontaneously Hypertensive and Normotensive Wistar-Kyoto Rats.

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