Influence of Aging on the Relaxant Responses to ω–3 Fatty Acids in Fischer 344 Rat Aorta

Abstract

The effect of age on the vasorelaxant properties of the ω-3 fatty acids, docosahexaenoic (DHA) and eicosapentaenoic (EPA), in isolated rat aortic rings were investigated in 4–, 15– and 24-month-old Fischer 344 rats. Increased aortic wall thickness was seen in both 15- and 24-month-old rats. Maximal contractile responses to norepinephrine (NE) were greater in intact and de-endothelialized (ENDO–) rings from 15- and 24-month-old rats; although increased sensitivity to NE was exhibited in 4-month-old rings. DHA- and EPA–induced (1-100 μmol/l) responses were similar between the three age groups in intact rings. Removal of the endothehum enhanced relaxant responses to both DHA and EPA in all three groups. EPA-induced (1-100 μmol/l) responses ranged from –4 to –28% for both 4– and 15–month ENDO– rings and -1 to -18% in 24-month ENDO–rings. DHA ENDO– ring responses (1–100 μmol/l) were -4 to -13% in 4 months, -5 to -23% in 15 months, and -0.8 to -16% in 24 months. Age differences were apparent with the ENDO– ring responses to DHA and EPA. These differences were seen with greater relaxant responses to both EPA and DHA in the 4- and 15-month-old aortic rings. Increased sensitivity and a greater maximal relaxant response to acetylcholine (ACH) was noted in the 15-month-old group. Four- and 24-month rings exhibited similar sensitivity and maximal relaxant responses to ACH. However, relaxation was decreased in 24-month rings at low ACH concentrations. These findings suggest that both functional and morphological changes occur with aging. DHA– and EPA–induced responses are not altered by aging in intact rings; however, removal of the endothehum enhances their vasorelaxant properties in all three age groups. This may be related to the direct actions of DHA and EPA on vascular smooth muscle, rather than on mechanisms associated with generation of endothelium-derived relaxing factor.

Selective and potent inhibitory effect of docosahexaenoic acid (DHA) on U46619-induced contraction in rat aorta

“…These circulatory-protective effects of fish oil may be partly ascribed to the blood vessel relaxation attained with DHA and/or EPA. In support of this presumption, both DHA and EPA were reported to produce relaxant responses in isolated vascular tissues (10,11,12,13). However, in these studies, the relaxant effects of DHA and EPA were mainly examined against the contractions induced by α-adrenoceptor stimulation or by depolarizing high-KCl solution.…”

“…However, in regard to DHA, it has not been conclusively determined whether the vascular effects of DHA significantly involve the endothelium. For instance, some groups have reported vascular smooth muscle-direct blood vessel relaxation by DHA (12, 14, 25, 26). In contrast, a significant role for the endothelium has been suggested in DHA-induced vascular relaxation.…”

Adult cardiorenal benefits from postnatal fish oil supplement in rat offspring of low-protein pregnancies

“…Randomized trials suggest an antihypertensive effect of high intakes of fish oil, especially in older populations and in hypertensive populations (Geleijnse et al, 2002). This effect may be mediated by the vasorelaxant response of eicosapentaenois acid (EPA, 20: 5n-3) and docosahexaenoic acid (DHA,, as demonstrated in rat models of hypertension (Engler et al, 1999), hypercholesterolemia, and balloon arterial injury (Engler et al, 1999), and aging (Engler and Engler, 1996).…”

Pharmacological Characteristics of the Inhibitory Effects of Docosahexaenoic Acid on Vascular Contractions Studied in Rat Mesenteric Artery

“…In addition, an obligatory role of the endothelium in EPA-induced relaxation was proposed for rabbit and cat aorta [25]. By contrast, a direct relaxation of the vascular smooth muscle to DHA has also been reported [13,14,16,26]. Therefore, at the beginning of this study, we examined whether the inhibitory effect of DHA on U46619 required the presence of endothelium.…”

“…In support of this presumption concerning the significant roles for DHA in causing blood vessel relaxation, this ω-3 PUFA has been reported to induce relaxant responses in isolated vascular tissues [11,12,13,14,15]. However, these earlier studies mainly focused on DHA effects on contractions mediated by α-adrenoceptor or membrane depolarization.…”