BACKGROUND: Chronic treatment with the dietary flavonoid quercetin is known to lower blood pressure and restore endothelial dysfunction in animal models of hypertension. This study investigated the direct effects of quercetin on vascular response in chronic 2-kidney, 1-clip (2K1C) renal hypertensive rats. The effects of antioxidant vitamin ascorbic acid on the vasoreactivity were also examined. METHODS: 2K1C renal hypertension was induced by clipping the left renal artery; age-matched rats that received sham treatment served as controls. Thoracic aortae were mounted in tissue baths for the measurement of isometric tension. RESULTS: Relaxant responses to acetylcholine were significantly attenuated in 2K1C rats in comparison with sham rats. Quercetin or ascorbic acid augmented acetylcholine-induced relaxation in 2K1C rats, whereas no significant differences were noted in sham rats. The relaxation response to sodium nitroprusside was comparable between 2K1C and sham rats, and sodium nitroprusside-induced relaxation was not altered by quercetin or ascorbic acid in either group. The contractile response to phenylephrine was significantly enhanced in 2K1C rats compared with sham rats. Phenylephrine-induced contraction was inhibited by pretreatment with quercetin or ascorbic acid in 2K1C rats, whereas neither chemical affected responses in sham rats. N(w)-nitro-L-arginine methyl ester markedly augmented the contractile response to phenylephrine in sham rats, whereas no significant differences were observed in 2K1C rats. Quercetin or ascorbic acid did not affect phenylephrine-induced contraction in the presence of N(w)-nitro-L-arginine methyl ester in either 2K1C or sham rats. CONCLUSION: Acute exposure to quercetin appears to improve endothelium-dependent relaxation and inhibit the contractile response, similar to the effect of ascorbic acid in 2K1C hypertension. These results partially explain the vascular beneficial effects of quercetin in renal hypertension.
Acetylcholine ; Animals ; Aorta* ; Aorta, Thoracic ; Ascorbic Acid ; Baths ; Blood Pressure ; Hypertension ; Hypertension, Renal ; Models, Animal ; Nitroprusside ; Phenylephrine ; Placebos ; Quercetin* ; Rats* ; Relaxation ; Renal Artery ; Sodium ; Vitamins

BACKGROUND: The plant-derived estrogen biochanin A is known to cause vasodilation, but its mechanism of action in hypertension remains unclear. This study was undertaken to investigate the effects and mechanisms of biochanin A on the thoracic aorta in two-kidney, one clip (2K1C) renovascular hypertensive rats. METHODS: Hypertension was induced by clipping the left renal artery, and control age-matched rats were sham treated. Thoracic aortae were mounted in tissue baths to measure isometric tension. RESULTS: Biochanin A caused concentration-dependent relaxation in aortic rings from 2K1C hypertensive and sham-treated rats, which was greater in 2K1C rats than in sham rats. Biochanin A-induced relaxation was significantly attenuated by removing the endothelium in aortic rings from 2K1C rats, but not in sham rats. Nomega-Nitro-L-arginine methylester, a nitric oxide synthase inhibitor, or indomethacin, a cyclooxygenase inhibitor, did not affect the biochanin A-induced relaxation in aortic rings from 2K1C and sham rats. By contrast, treatment with glibenclamide, a selective inhibitor of adenosine triphosphate-sensitive K+ channels, ortetraethy-lammonium, an inhibitor of Ca2+-activated K+ channels, significantly reduced biochanin A-induced relaxation in aortic rings from both groups. However, 4-aminopyridine, a selective inhibitor of voltage-dependent K+ channels, inhibited the relaxation induced by biochanin A in 2K1C rats, whereas no significant differences were observed in sham rats. CONCLUSION: These results suggest that the enhanced relaxation caused by biochanin A in aortic rings from hypertensive rats is endothelium dependent. Vascular smooth muscle K+ channels may be involved in biochanin A-induced relaxation in aortae from hypertensive and normotensive rats. In addition, an endothelium-derived activation of voltage-dependent K+ channels contributes, at least in part, to the relaxant effect of biochanin A in renovascular hypertension.
4-Aminopyridine ; Adenosine ; Animals ; Aorta ; Aorta, Thoracic ; Baths ; Endothelium ; Estrogens ; Glyburide ; Hypertension ; Hypertension, Renovascular ; Indomethacin ; Muscle, Smooth, Vascular ; Nitric Oxide Synthase ; Phytoestrogens* ; Potassium Channels, Calcium-Activated ; Prostaglandin-Endoperoxide Synthases ; Rats* ; Relaxation ; Renal Artery ; Vasodilation*

BACKGROUND: Endothelial dysfunction is linked to exaggerated production of superoxide anions. This study was conducted to examine the effects of oxidative stress on endothelial modulation of contractions in chronic two-kidney, one-clip (2K1C) renal hypertensive rats. METHODS: The 2K1C hypertension was induced by clipping the left renal artery; age-matched rats receiving sham treatment served as controls. Thoracic aortae were isolated and mounted in tissue baths for measurement of isometric tension. RESULTS: Norepinephrine-induced contraction was augmented by the removal of the endothelium, which was more pronounced in sham rats than in 2K1C rats. Nomega-nitro-L-arginine methyl ester, an inhibitor of nitric oxide production, had a similar augmenting effect. Vitamin C inhibited the contraction in aortic rings with intact endothelium from 2K1C rats but not from sham rats. The contraction was also suppressed by treatment with diphenyleneiodonium or apocynin, inhibitors of nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase, in the aortae with intact endothelium from 2K1C rats but not in those from sham rats. Superoxide anions generated by xanthine oxidase/hypoxanthine enhanced the contraction in the aortae with intact endothelium from sham rats, but had no effect in 2K1C rats. Enhanced contractile responses to norepinephrine by xanthine oxidase/hypoxanthine in sham rats were reversed by vitamin C. CONCLUSION: These results suggest that the effect on endothelial modulation of endothelium-derived nitric oxide is impaired in 2K1C hypertension. The impairment is, at least in part, related to increased production of superoxide anions by NADH/NADPH oxidase.
Adenine ; Animals ; Aorta* ; Aorta, Thoracic ; Ascorbic Acid ; Baths ; Endothelium ; Hypertension ; Hypertension, Renal ; Niacinamide ; Nitric Oxide ; Norepinephrine ; Oxidative Stress* ; Oxidoreductases ; Placebos ; Rats* ; Renal Artery ; Superoxides ; Xanthine

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of transradial percutaneous coronary intervention (TRI) compared with transfemoral percutaneous coronary intervention (TFI) in patients with ischemic heart disease. METHODS: We reviewed retrospectively the medical records including imaging data of the patients with ischemic heart disease who underwent TRI or TFI from January 2007 to December 2009 in Soonchunhyang University Seoul Hospital. We compared major adverse cardiac and cerebrovascular events (MACCEs) including death, myocardial infarction, revascularization, stent thrombosis, and cerebrovascular accident during follow-up period. We also compared procedure related vascular complications including hematoma, arteriovenous fistula, pseudoaneurysm, and infection. RESULTS: Total number of patients was 347 (256 patients of TRI and 91 patients of TFI). There were no significant differences in the rate of MACCEs between two groups. There were significantly less procedure-related vascular complications in TRI group (3.1% vs. 11.0%, P=0.010). CONCLUSION: TRI is as effective as TFI with no difference in the rate of MACCEs in patients with ischemic heart disease. TRI is superior to TFI in safety with reduction of vascular complications.
Aneurysm, False ; Arteriovenous Fistula ; Coronary Artery Disease ; Femoral Artery ; Follow-Up Studies ; Heart ; Hematoma ; Humans ; Medical Records ; Myocardial Infarction ; Myocardial Ischemia ; Percutaneous Coronary Intervention ; Radial Artery ; Retrospective Studies ; Stents ; Stroke ; Thrombosis

BACKGROUND: Ferulic acid (FA) is a naturally occurring nutritional compound. Although it has been shown to have antihypertensive effects, its effects on vascular function have not been intensively established. The aim of this study was to assess the vasoreactivity of FA in chronic two-kidney, one-clip (2K1C) renal hypertensive rats. METHODS: Hypertension was induced in 2K1C rats by clipping the left renal artery and age-matched rats that received a sham treatment served as a control. Thoracic aortas were mounted in tissue baths to measure isometric tension. The effects of FA on vasodilatory responses were evaluated based on contractile responses induced by phenylephrine in the aortic rings obtained from both 2K1C and sham rats. Basal nitric oxide (NO) bioavailability in the aorta was determined by the contractile response induced by NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). RESULTS: FA induced concentration-dependent relaxation responses which were greater in 2K1C hypertensive rats than in sham-clipped control rats. This relaxation induced by FA was partially blocked by the removal of endothelium or by pretreating with L-NAME. L-NAME-induced contractile responses were augmented by FA in 2K1C rats, while no significant differences were noted in sham rats. FA improved acetylcholine-induced endothelium-dependent vasodilation in 2K1C rats, but not in sham rats. The simultaneous addition of hydroxyhydroquinone significantly inhibited the increase in acetylcholine-induced vasodilation by FA. CONCLUSION: These results suggest that FA restores endothelial function by altering the bioavailability of NO in 2K1C hypertensive rats. The results explain, in part, the mechanism underlying the vascular effects of FA in chronic renal hypertension.
Animals ; Aorta ; Aorta, Thoracic ; Baths ; Biological Availability ; Coumaric Acids ; Endothelium ; Hydroquinones ; Hypertension ; Hypertension, Renal ; NG-Nitroarginine Methyl Ester ; Nitric Oxide ; Nitric Oxide Synthase ; Phenylephrine ; Placebos ; Rats ; Relaxation ; Renal Artery ; Salicylamides ; Vasodilation

PURPOSE: Thiazide diuretics exert their hypotensive efficacy through a combined vasodilator and diuretic effect. The present study was conducted to assess the inhibitory effect of thiazide diuretic, hydrochlorothiazide, and the thiazide-like diuretics, indapamide and chlorthalidone on contractile responses to norepinephrine and arginine vasopressin in aortic rings from 2K1C renal hypertensive and sham-clipped normotensive rats. METHODS: 2K1C hypertension was made by clipping the left renal artery and age-matched control rats received a sham treatment. Changes in the tension of aortic ring preparations were measured isometrically. RESULTS: Indapamide inhibits the contractile responses to norepinephrine and vasopressin in aortic rings from 2K1C rats, while it did not modify in control rats. The inhibitory effect of indapamide was abolished by endothelium removal. Hydrochlorothiazide or chlorthalidone did not affect the vasoconstriction induced by norepinephrine and vasopressin either in sham or in 2K1C hypertensive rats. CONCLUSION: These results suggest that indapamide inhibits the contractile responses to norepinephrine and vasopressin via an endothelium-dependent mechanism in 2K1C renal hypertension.
Animals ; Aorta ; Arginine Vasopressin ; Chlorthalidone ; Diuretics ; Endothelium ; Hydrochlorothiazide ; Hypertension ; Hypertension, Renal ; Indapamide ; Norepinephrine ; Placebos ; Rats ; Renal Artery ; Salicylamides ; Sodium Chloride Symporter Inhibitors ; Vasoconstriction ; Vasodilation ; Vasopressins

PURPOSE: Evidence has emerged that oxygen-derived free radicals may induce vascular relaxations via ATP-sensitive K+ (K(ATP)) channels and the level of free radicals is increased in animal models of hypertension. The present study was conducted to determine whether relaxations to an K(ATP) channel opener, pinacidil, are increased in the aorta from two-kidney, one clip (2K1C) hypertensive rats and whether free radial scavengers reduce these relaxations. METHODS: 2K1C hypertension was induced by clipping the left renal artery and age-matched control rats received a sham treatment. Rings of aortae without endothelium were suspended for isometric force recording. RESULTS: Relaxations to pinacidil (10(-8) to 10(-5) M), which are abolished by glibenclamide (10(-5) M), were augmented in the aorta from 2K1C rats, compared to those from control rats. In the aorta from 2K1C rats, catalase (1,200 U/mL), but neither superoxide dismutase (150 U/mL) nor deferoxamine (10(-4) M), reduced relaxations to pinacidil, whereas in the aorta from control rats, the free radical scavengers did not affect these relaxations. CONCLUSION: These results suggest that in 2K1C hypertension, vasorelaxation to an KATP channel opener is augmented and that hydrogen peroxide in smooth muscle cells may partly contribute to these relaxations.
Animals ; Aorta ; Catalase ; Deferoxamine ; Endothelium ; Free Radical Scavengers ; Free Radicals ; Glyburide ; Hydrogen Peroxide ; Hypertension ; Hypertension, Renal ; Models, Animal ; Myocytes, Smooth Muscle ; Pinacidil ; Placebos ; Rats ; Relaxation ; Renal Artery ; Salicylamides ; Superoxide Dismutase ; Vasodilation

PURPOSE: Baroreceptor reflex regulation has been shown to reset towards a higher blood pressure level. This study was designed to assess alterations of chronotropic baroreflexes in two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. METHODS: Arterial pressure and heart rate (HR) were monitored continuously during intravenous infusions of phenylephrine or sodium nitroprusside. Ensuing reflex HR responses during each drug infusion were determined in two ways: (a) at 10 s intervals (time analysis), and (b) with every 10 mmHg change in pressure (pressure analysis). RESULTS: Both pressor and depressor responses produced by phenylephrine or sodium nitroprusside were comparable between normotensive and hypertensive rats. Both reflex tachycardia and bradycardia were attenuated in 2K1C hypertensive rats as compared with normotensive rats, whereas no significant differences were shown in DOCA-salt hypertensive rats. CONCLUSION: These results indicate that chronotropic baroreflexes are impaired in 2K1C hypertensive rats, but not in DOCA-salt hypertensive rats.
Animals ; Arterial Pressure ; Baroreflex ; Blood Pressure ; Bradycardia ; Desoxycorticosterone ; Dihydrotachysterol ; Heart Rate ; Hypertension ; Infusions, Intravenous ; Nitroprusside ; Phenylephrine ; Rats ; Reflex ; Tachycardia

PURPOSE: Hypertension may be involved an alteration of intrinsic basal tone in vascular smooth muscle. The purpose of this study was to investigate the vasorelaxant effect of atrial natriuretic peptide (ANP) on isolated non-contracted aorta from two-kidney, one clip (2K1C) renovascular hypertensive rats. METHODS: 2K1C hypertension was induced by clipping the left renal artery and were used 6 weeks later. Age-matched rats receiving a sham treatment, which served as controls. The thoracic aortae were mounted in tissue baths to measure the isometric tension. RESULTS: ANP diminished basal tone in previously unstimulated thoracic aortic rings from 2K1C hypertensive rats, while it had no effect in the control rats. Endothelial destruction potentiated the vasorelaxant effect of ANP on basal tone in 2K1C rats. A similar potentiation of the ANP response was observed by pre-treatment with N omega-nitro-L-arginine methyl ester (L-NAME) or methylene blue in aortic rings with endothelium. Treatment with calcium-free Krebs decreased basal tone and abolished ANPresponse. These effects were observed only in aortic rings from 2K1C rats. Similarly, staurosporine and calphostin C, inhibitors of protein kinase C (PKC), lowered basal tone and abolished ANP-response in hypertensive rats. CONCLUSION: These results demonstrate that ANP has a vasorelaxant effect on basal tone in 2K1C renovascular hypertension. Inhibition of ANP effects on basal tone by calcium-free Krebs and PKC antagonists suggests that altered Ca2+ -active tone is involved in hypertension, that modifies the response of vascular smooth muscle to the ANP.
Animals ; Aorta ; Aorta, Thoracic ; Atrial Natriuretic Factor ; Baths ; Endothelium ; Hypertension ; Hypertension, Renovascular ; Methylene Blue ; Muscle, Smooth, Vascular ; Naphthalenes ; NG-Nitroarginine Methyl Ester ; Placebos ; Protein Kinase C ; Rats ; Renal Artery ; Salicylamides ; Staurosporine

PURPOSE: S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide (NO) donor, is thought to relax vascular smooth muscle by stimulation of soluble guanylate cyclase, accumulation of its product cyclic GMP (cGMP) level. Evidence has emerged that NO-induced vasodilatation is also mediated by stimulating Ca2+-activated K+ (KCa) channels directly or indirectly through cGMP. The aim of the present study was to investigate possible involvement or alteration of KCa channels in the mechanism of vasodilation induced by SNAP in two-kidney, one-clip (2K1C) hypertensive rats. METHODS: 2K1C hypertension was made by clipping the left renal artery and age-matched control rats received a sham treatment. Using rings prepared from thoracic aortae, we studied changes in isometric tension of the rings in response to SNAP to evaluate effects of a soluble guanylate cyclase inhibitor methylene blue (MB), and a specific blocker of KCa channel iberiotoxin (ITX). RESULTS: Aortic rings from 2K1C hypertensive and sham-clipped control rats precontracted with phenylephrine showed similar relaxation to SNAP. MB markedly suppressed the SNAP-induced relaxation in both groups, leaving about 30% of MB-resistant relaxation. ITX nearly completely eliminated the MB-resistant relaxation in control rats, but it did not affect 2K1C rats. CONCLUSION: These results suggest that SNAP-induced vasorelaxation is mediated through cGMP- dependent and cGMP-independent KCa channel involving mechanisms, the latter may be altered in 2K1C renal hypertension.
Animals ; Aorta* ; Aorta, Thoracic ; Cyclic GMP ; Guanylate Cyclase ; Humans ; Hypertension ; Hypertension, Renal ; Methylene Blue ; Muscle, Smooth, Vascular ; Nitric Oxide ; Phenylephrine ; Placebos ; Potassium Channels, Calcium-Activated ; Rats* ; Relaxation* ; Renal Artery ; S-Nitroso-N-Acetylpenicillamine ; Tissue Donors ; Vasodilation