RESUMO
The purpose of the present study was to examine the effects of dietary supplementation of arachidonic acid (ARA) on age-related changes in endothelium-dependent vascular responses. Young male Fisher-344 rats (2-mo-old) and aged rats of the same strain (22-mo-old) were randomly separated into a control diet group (young control, YC; old control, OC) and an ARA-containing diet group (young ARA, YA; old ARA, OA). After a 2-mo feeding period, vascular responses were evaluated using both endothelium-intact and -denuded aortic rings. Phenylephrine (alpha1-adrenoceptor agonist)-induced vasoconstrictor responses in endothelium-intact rings from group OC tended to be augmented compared with those of rings from groups YC and YA, although this augmentation was significantly suppressed by dietary supplementation of ARA. There were no significant differences in vascular responses to phenylephrine in endothelium-denuded rings among groups YC, YA, OC, and OA. Acetylcholine (Ach)-induced, endothelium-dependent vasorelaxation was attenuated in groups OC and OA compared with that in groups YC and YA. ARA supplementation induced slight enhancement of Ach-induced vasorelaxation in aged rats. Ach-induced vasorelaxation correlated very well with aortic ARA concentration in aged rats, but not in young rats. There were no significant differences in endothelium-independent vasodilator responses to sodium nitroprusside in endothelium-denuded rings among groups YC, YA, OC, and OA. These findings suggest that dietary ARA supplementation improves the age-related endothelial dysfunction that leads to various cardiovascular diseases.
Assuntos
Ácido Araquidônico/farmacologia , Suplementos Nutricionais , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Acetilcolina/metabolismo , Acetilcolina/farmacologia , Fatores Etários , Análise de Variância , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/metabolismo , Aorta Torácica/fisiopatologia , Ácido Araquidônico/metabolismo , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Endotélio Vascular/metabolismo , Masculino , Modelos Animais , Nitroprussiato/farmacologia , Fenilefrina/metabolismo , Fenilefrina/farmacologia , Ratos , Ratos Endogâmicos F344 , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/metabolismo , Vasoconstritores/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/metabolismo , Vasodilatadores/farmacologiaRESUMO
Sesame peptide powder (SPP) exhibited angiotensin I-converting enzyme (ACE) inhibitory activity, and significantly and temporarily decreased the systolic blood pressure (SBP) in spontaneously hypertensive rats (SHRs) by a single administration (1 and 10 mg/kg). Six peptide ACE inhibitors were isolated and identified from SPP. The representative peptides, Leu-Val-Tyr, Leu-Gln-Pro and Leu-Lys-Tyr, could competitively inhibit ACE activity at respective Ki values of 0.92 microM, 0.50 microM, and 0.48 microM. A reconstituted sesame peptide mixture of Leu-Ser-Ala, Leu-Gln-Pro, Leu-Lys-Tyr, Ile-Val-Tyr, Val-Ile-Tyr, Leu-Val-Tyr, and Met-Leu-Pro-Ala-Tyr according to their content ratio in SPP showed a strong antihypertensive effect on SHR at doses of 3.63 and 36.3 microg/kg, which accounted for more than 70% of the corresponding dosage for the SPP-induced hypotensive effect. Repeated oral administration of SPP also lowered both SBP and the aortic ACE activity in SHR. These results demonstrate that SPP would be a beneficial ingredient for preventing and providing therapy against hypertension and its related diseases.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Hipertensivos/farmacologia , Hipertensão/enzimologia , Oligopeptídeos/farmacologia , Peptidil Dipeptidase A/efeitos dos fármacos , Sesamum/química , Administração Oral , Sequência de Aminoácidos , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/isolamento & purificação , Animais , Anti-Hipertensivos/química , Anti-Hipertensivos/isolamento & purificação , Pressão Sanguínea/efeitos dos fármacos , Hidrólise , Oligopeptídeos/química , Oligopeptídeos/isolamento & purificação , Preparações de Plantas/administração & dosagem , Preparações de Plantas/química , Proteínas de Plantas/química , Proteínas de Plantas/isolamento & purificação , Ratos , Ratos Endogâmicos SHRRESUMO
In the present study, we evaluated the relationship between the antihypertensive effect of sesamin, a lignan from sesame oil, and its antioxidative activity in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. After a 5-week treatment period, systolic blood pressure was significantly elevated in normal diet-fed DOCA-salt animals compared with cases in sham-operated animals. Sesamin feeding, tempol (a superoxide dismutase mimetic) treatment or antihypertensive drugs combination (triple therapy; reserpine, hydralazine, hydrochlorothiazide) significantly suppressed the development of DOCA-salt-induced hypertension. Compared with sham-operated rats, the normal diet-fed DOCA-salt rats revealed marked increases in aortic superoxide (O(2)(-)) production. These increases in O(2)(-) production were significantly suppressed by sesamin feeding or tempol treatment, but not by triple therapy. Acetylcholine (Ach)-induced endothelium-dependent relaxation was markedly decreased in normal diet-fed DOCA-salt rats, compared with cases in sham-operated rats. Sesamin feeding and triple therapy significantly improved the DOCA-salt-induced impairment of endothelium-dependent relaxation. However, tempol treatment had no effect on the impaired vasodilator responses induced by DOCA-salt treatment. In DOCA-salt rats with or without sesamin feeding, systolic blood pressure significantly correlated with both aortic O(2)(-) production and endothelium-dependent vascular relaxation. These findings suggest that sesamin feeding inhibits the enhancement of aortic O(2)(-) production in DOCA-salt hypertensive rats, and this effect may contribute to the antihypertensive effect of sesamin. Sesamin feeding-induced improvement of endothelial dysfunction seems to result from the above antioxidative and antihypertensive effects.