Young Mi Kwon

Antihypertensive Effect of All-cis-5,8,11,14,17-Icosapentaenoate of Aged Rats Is Associated with an Increase in the Release of ATP from the Caudal Artery

Fish oils have been shown to lower blood pressure in hypertensive subjects. All-cis-5,8,11,14,17-icosapentaenoate (EPA), one of the ω–3 polyunsaturated fatty acids, is known to be one of the major active components in fish oil that has beneficial effects on the cardiovascular system. However, little is known about the antihypertensive effect of EPA alone on blood pressure. In the present study, we have determined the spontaneous and noradrenaline-evoked release of ATP, ADP, AMP, and adenosine from caudal arteries of aged (100 weeks old) Wistar rats which were fed a standard diet or a high cholesterol diet, treated with EPA. Dietary EPA administration increased plasma and caudal arterial EPA concentrations and repressed increases in blood pressure with advancing age in both aged rats with and without hypercholesterolemia. In addition, noradrenaline (1 µmol/l) evoked a significantly greater release of purines from the caudal arteries of EPA-administered aged rats compared to both sets of control rats. Regression analysis revealed a significant relationship between the total amount of purines released from the artery and blood pressure. These results suggest that administration of EPA to aged rats increases the release of ATP from the vascular endothelial cells, leading to repression of the blood pressure rise seen with advancing age.

Hypotension induced by exercise is associated with enhanced release of adenyl purines from aged rat artery

To determine whether the antihypertensive effects of exercise are associated with release of ATP and its metabolites from arteries, we assayed blood pressure and the release of adenine nucleotides and nucleosides from the caudal arteries of exercised and sedentary aged hypercholesterolemic rats. Exercise on a treadmill for 12 wk significantly decreased the rise in systolic and diastolic blood pressure by 7.5 and 15.9%, respectively, with advanced age. The concentrations of oleic, linoleic, and linolenic acids in the caudal artery decreased significantly with exercise, demonstrating an association between exercise and the unsaturation index of caudal arterial fatty acids. The amounts of total adenyl purines released by the arterial segments from exercised rats, both spontaneously and in response to norepinephrine, were significantly greater by 80.0 and 60.7%, respectively, than those released by tissues from sedentary rats. These results suggest that exercise alters the membrane fatty acid composition in aged rats as well as the release of ATP from vascular endothelial cells and that these factors are associated with the regression of the rise in blood pressure normally observed with advanced age.To determine whether the antihypertensive effects of exercise are associated with release of ATP and its metabolites from arteries, we assayed blood pressure and the release of adenine nucleotides and nucleosides from the caudal arteries of exercised and sedentary aged hypercholesterolemic rats. Exercise on a treadmill for 12 wk significantly decreased the rise in systolic and diastolic blood pressure by 7.5 and 15.9%, respectively, with advanced age. The concentrations of oleic, linoleic, and linolenic acids in the caudal artery decreased significantly with exercise, demonstrating an association between exercise and the unsaturation index of caudal arterial fatty acids. The amounts of total adenyl purines released by the arterial segments from exercised rats, both spontaneously and in response to norepinephrine, were significantly greater by 80.0 and 60.7%, respectively, than those released by tissues from sedentary rats. These results suggest that exercise alters the membrane fatty acid composition in aged rats as well as the release of ATP from vascular endothelial cells and that these factors are associated with the regression of the rise in blood pressure normally observed with advanced age.

Cigarette smoke-modified low density lipoprotein impairs endothelium-dependent relaxation in isolated rabbit arteries

1. We investigated the effects of cigarette smoke-modified low-density lipoprotein (CS-LDL) on endothelium-dependent relaxations in various isolated rabbit arteries, and compared them with those of oxidized LDL (Ox-LDL). 2. In aorta rings, acetylcholine-induced endothelium-dependent relaxations were attenuated by preincubation with CS-LDL and Ox-LDL. Endothelium-independent relaxations induced by sodium nitroprusside were not modified. Similar changes were observed in rings of coronary and basilar arteries. 3. These findings indicate that CS-LDL, as well as Ox-LDL, may decrease the release or activity of endothelium-derived relaxing factor in vascular endothelial cells.

Long-term supplementation with a high cholesterol diet decreases the release of ATP from the caudal artery in aged rats

We examined the effects of high cholesterol (HC) diet on the spontaneous and noradrenaline-induced release of ATP, ADP, AMP and adenosine from caudal arteries and on the plasma levels of these adenyl purines in aged (100-week-old) Wistar rats. Administration of this diet for 12 weeks significantly reduced spontaneous and noradrenaline (1 micromol/L)-evoked release of adenyl purines from the caudal arteries relative to rats given the control diet The unsaturation index of fatty acids (UI), which gives the average number of double bonds, of both the plasma and the caudal artery was significantly less in the HC diet-fed rats than in those fed the control diet. The HC diet for 12 weeks produced a slight but significant increase in systolic and diastolic blood pressure with advancing age. Regression analysis revealed a significant inverse relationship between the total amount of purines released from the artery and diastolic blood pressure, and also a positive relationship between the total amount of purines released and the UI of the caudal artery. These results suggest that the high cholesterol diet decreased the release of adenyl purines from the caudal arteries of aged rats, leading to an increase in blood pressure.

BOTH EXTRACELLULAR ATP AND SHEAR STRESS REGULATE THE RELEASE OF NITRIC OXIDE IN RAT CAUDAL ARTERY

1. To elucidate the physiological role of nitric oxide (NO) in regulating vascular tone, the effects of NG‐nitro‐L‐arginine methyl ester (L‐NAME), an NO synthase inhibitor, on the vasoconstrictor response to noradrenaline (NA) in rat caudal artery was examined.

Dietary cholesterol enhances impaired endothelium-dependent relaxations in aortas of salt-induced hypertensive Dahl rats

We investigated the effect of hypercholesterolemia on the vascular reactivity of thoracic aortas isolated from hypertensive Dahl salt-sensitive (DS) rats. DS rats were fed on a low-sodium diet (control group), a low-sodium plus high-cholesterol diet (CHOL group), a high-sodium diet (NaCl group) or a high-sodium plus high-cholesterol diet (NaCl + CHOL group) for 8 weeks. Hypercholesterolemia developed in the CHOL and NaCl + CHOL groups, while hypertension developed in the NaCl and NaCl + CHOL groups, with these changes being greatest in the NaCl + CHOL group. Aortic cholesteryl ester accumulation was attenuated in the aortic rings from the NaCl and NaCl + CHOL groups, compared to the control group. The degree of attenuation in the NaCl + CHOL group was significantly greater than that in the NaCl group. Endothelium-dependent relaxations induced by the calcium ionophore A23187 were attenuated only in the NaCl + CHOL group. Endothelium-independent relaxations in response to sodium nitroprusside were slightly but significantly attenuated in the NaCl + CHOL group. The relaxations in the CHOL group were comparable to those in the control group. These findings indicate that cholesterol feeding strikingly enhances the impaired endothelium-dependent relaxations and the slightly impaired endothelium-independent relaxations in the aorta of DS rats with salt-induced hypertension, parallel to the development of hypertension, hypercholesterolemia and cholesterol deposition.

Comparison of the effects of hypercholesterolaemia on relaxation responses in aortas of spontaneously hypertensive rats and Dahl salt-sensitive rats.

1. We investigated the effects of hypercholesterolaemia on relaxation responses in thoracic aortas isolated from two different types of hypertensive rats; spontaneously hypertensive rats (SHR) and Dahl salt‐sensitive rats (DSR).

DIFFERENT CHOLESTEROL DEPOSITION IN AORTA OF DAHL SALT‐SENSITIVE RATS AND SPONTANEOUSLY HYPERTENSIVE RATS FED A HIGH‐CHOLESTEROL DIET

1. We compared the serum and aortic lipid levels in spontaneously hypertensive rats (SHR) and Dahl salt‐sensitive rats (DSR) fed a high‐cholesterol (HC) diet.