The Hypotensive Effect of Docosahexaenoic Acid Is Associated with the Enhanced Release of ATP from the Caudal Artery of Aged Rats

Abstract

Fish oils have been shown to lower blood pressure in hypertensive subjects. To determine the mechanism of this hypotensive effect, we examined the effects of docosahexaenoic acid (DHA), one of the (n-3) polyunsaturated fatty acids in fish oil, on blood pressure and on the release of adenyl purines, such as ATP, ADP, AMP and adenosine, from the caudal arteries of aged rats. Aged female Wistar rats (100 wk) were fed a high cholesterol diet and were administered intragastrically ethyl all-cis-4,7,10,13,16,19-docosahexaenoate [300 mg/(kg.d)] for 12 wk (DHA group) or vehicle alone (control group). Compared with the controls, rats supplemented with DHA had significantly greater (10.1%) DHA concentrations in the caudal arteries. This was associated with more total (n-3) arterial fatty acids, a greater unsaturation index of arterial fatty acids, 43.9% lower plasma noradrenaline levels and the repression of the elevation in blood pressure observed with advancing age. The amount of purines released, both spontaneously and in response to noradrenaline, from arterial segments of DHA-supplemented rats was significantly higher than that released from tissues of control rats. Regression analysis revealed significant negative relationships between the total amount of purines released from the artery and the systolic (SBP) and diastolic (DBP) blood pressures. These results suggest that in aged rats, supplementation with DHA alters the membrane fatty acid composition as well as the amount of ATP released from vascular endothelial cells and decreases plasma noradrenaline, and that these factors may ameliorate the rise in blood pressure normally associated with advancing age.

Naturally occurring monoepoxides of eicosapentaenoic acid and docosahexaenoic acid are bioactive antihyperalgesic lipids

“…EpDPE and EpETE, much like the EET, activate big conductance calcium-activated potassium channels (BK Ca ), which can lead to hyperpolarization, thus relaxation of vascular smooth muscle cells (18)(19)(20). The antihypertensive, antithrombotic, and anti-atherosclerotic properties of EpDPE and EpETE have been demonstrated in multiple rat models (21)(22)(23). Furthermore, in vitro, the EETs, EpDPE, and EpETE inhibit platelet aggregation at concentrations below those affecting thromboxane synthesis ( 24 ), suggesting that these natural oxiranes have strong, selective, and possibly specifi c bioactivities.…”

The Pharmacology of the Cytochrome P450 Epoxygenase/Soluble Epoxide Hydrolase Axis in the Vasculature and Cardiovascular Disease

“…Biologic activity has been attributed to almost all of these P450 derivatives, which, just like the EETs, are reported to activate large-conductance calcium-activated potassium (BK) channels, leading to the hyperpolarization and relaxation of vascular smooth muscle cells (VSMCs) (Lauterbach et al, 2002;Ye et al, 2002;Morin et al, 2009). Moreover, the EEQs and EDPs demonstrate cardiovascular-protective properties, have been linked with angiogenesis and improved wound healing (Liclican and Gronert, 2010;Tian et al, 2010), and also show antihypertensive, antithrombotic, and antiatherosclerotic effects in several rat models (McLennan et al, 1996;Hashimoto et al, 1999;Frenoux et al, 2001). However, the specific enzymes involved in the conversion of linoleic acid, EPA, and DPA are less well studied than those that metabolize arachidonic acid, especially in relation to their effects on cardiovascular homeostasis (Oliw et al, 1996;Bylund et al, 1998a,b) and EPA and DPA "antagonists" have not been widely tested.…”

Characteristics of contractile activity in the renal artery of ovariectomized rats

“…Fatty acid composition was determined to estimate the 17β-estradiol effect on the uterus and the aorta using the one-step chromatographic analysis of Lepage and Roy (1986) described previously (Hashimoto et al, 1999). The protein concentration was estimated using the method of Lowry et al (1951).…”