Altered Aortic Production of 6-Keto-Prostaglandin F_1αfrom Aldosterone-Salt Hypertensive Rats

Abstract

Supersensitivity of vascular smooth muscle to catecholamines in aldosterone-salt hypertensive rats appears to reside beyond the α₁-adrenoceptor. The objective of this study was to assess the norepinephrine-stimulated production of arachidonic acid metabolites by aorta from control-salt rats (CSR) and aldosterone-salt hypertensive rats (AHR) to determine whether these metabolites might contribute to the altered sensitivity. Norepinephrine increased in a time-dependent manner the production of 6-keto-prostaglandin F α₁ (6-keto-PGF α₁), thromboxane B₂ (TXB₂) and prostaglandin E₂ (PGE₂) by the aortae of CSR. Production was an α₁-adrenoceptor-mediated event since it was inhibited greatly by prazosin but not by yohimbine. Basal values of the metabolites did not differ for 6-keto-PGF α₁ and TXB₂, but were higher in AHR compared with CSR for PGE₂. The norepinephrine concentration-response curve for 6-keto-PGF α₁ was shifted significantly to the right for the AHR group compared with CSR (EC₅₀ = 2.30 + 0.55 and 0.29 ± 0.07 µM, respectively) indicating decreased production of norepinephrine-stimulated prostaglandin I₂ in AHR. The norepinephrine-stimulated TXB₂ concentration-response curves for AHR and CSR were similar. Indomethacin was an effective inhibitor of TXB₂and 6-keto-PGF ₁α production in both. Norepinephrine-stimulated contraction was significantly affected by indomethacin in CSR but not in AHR. Whereas we observed an attenuation of a norepinephrine-stimulated vasodilatory substance in aortae of AHR compared with CSR, the effect of attenuation on vascular activity is presently unclear.

Preventive dietary potassium supplementation in young salt-sensitive Dahl rats attenuates development of salt hypertension by decreasing sympathetic vasoconstriction

“…1981, Uehara et al. 1987, 1990) due to noradrenaline‐induced stimulation of vascular PGI 2 synthesis and release (Jones et al. 1992).…”

Vasodilator efficiency of endogenous prostanoids, Ca2+-activated K+ channels and nitric oxide in rats with spontaneous, salt-dependent or NO-deficient hypertension

“…15,16 Thus, our data on the enhanced indomethacin-induced BP rise in conscious hypertensive rats, as well as a highly significant positive correlation (Figure 7b) between the indomethacin-induced BP rise and the basal BP level, represent a direct confirmation of the validity of the above data under the in vivo conditions. Interestingly, Jones et al 27 reported that norepinephrine, through its alpha 1 -adrenergic mechanisms, stimulated the in vitro production of PGI 2 , prostaglandin E2 and thromboxane A2 in the aorta of saltloaded rats, and this prostanoid formation was effectively inhibited by indomethacin, which also shifted the contractile dose-response curve to higher norepinephrine concentrations. When we examined the relationships between sympathetic vasoconstriction and prostanoiddependent vasodilatation in our set of experimental animals, we found a highly significant correlation between the magnitude of the pentolinium-induced BP fall and the indomethacin-induced BP rise (r¼0.599, n¼53, Po0.0001), which is in good agreement with the in vitro findings of Jones et al 27 There was a closer correlation between the basal BP and the pentolinium-induced BP fall than with the indomethacin-induced BP rise (Figures 7a and b), supporting the primary importance of sympathetic hyperactivity for the maintenance of high BP.…”