Salvia fruticosa Induces Vasorelaxation In Rat Isolated Thoracic Aorta: Role of the PI3K/Akt/eNOS/NO/cGMP Signaling Pathway

Abstract

Salvia fruticosa (SF) Mill. is traditionally used for its antihypertensive actions. However, little is known about its pharmacologic and molecular mechanisms of action. Here we determined the effects of an ethanolic extract of SF leaves on rings of isolated thoracic aorta from Sprague-Dawley rats. Our results show that SF extract increased nitric oxide production and relaxed endothelium-intact rings in a dose-dependent (0.3 µg/ml–1 mg/ml) manner, and the maximum arterial relaxation (Rmax) was significantly reduced with endothelium denudation. Pretreatment of endothelium-intact rings with L-NAME (a non-selective inhibitor of nitric oxide synthase, 100 µM), or ODQ (an inhibitor of soluble guanylyl cyclase, 10 µM) significantly diminished SF-mediated vasorelaxation. Furthermore, SF induced Akt phosphorylation as well as increased cGMP levels in rings treated with increasing doses of SF. Prior exposure to PI3K inhibitors, wortmannin (0.1 µM) or LY294002 (10 µM), decreased cGMP accumulation and attenuated the SF-induced vasorelaxation by approximately 50% (Rmax). SF-evoked relaxation was not affected by indomethacin, verapamil, glibenclamide, tetraethylammonium, pyrilamine or atropine. Taken together, our results indicate that SF induces endothelium-dependent vasorelaxation through the PI3K/Akt/eNOS/NO/sGC/cGMP signaling pathway. Our data illustrate the health-orientated benefits of consuming SF which may act as an antihypertensive agent to reduce the burden of cardiovascular complications.

Rhus coriaria L. (Sumac) Evokes Endothelium-Dependent Vasorelaxation of Rat Aorta: Involvement of the cAMP and cGMP Pathways

“…The buffer was continuously aerated with 5% CO 2 in oxygen to maintain the pH of KHB at 7.4. The rings were equilibrated for an hour, subjected to a stepwise increase in tension of 0.5 g every 15 min till a final resting tension of 2 g was attained, subsequent to each incremental rise in tension the rings were washed with fresh buffer ( Anwar et al, 2017 ). Tension changes in aortic ring responses were recorded by a computerized PowerLab data acquisition system (AD Instruments, United Kingdom).…”

“…To decipher the signaling routes, each aortic ring was contracted with a suboptimal value of 3 μM NE, on attaining a plateau (approximately 3 min), cumulative dose response curve (CDRC) to sumac was constructed in the absence or presence of various pharmacological inhibitors ( Anwar et al, 2013 , 2017 ): L -NAME (100 μM), ODQ (10 μM), indomethacin (10 μM), glibenclamide (10 μM), TEA (100 μM), triciribine (10 μM), wortmannin (100 nM), LY294002 (10 μM), SQ22536 (100 μM), or a vehicle control. In addition to the above set of experimental data, Rhus coriaria extract (RCE)-induced arterial relaxation was determined in endothelium-denuded segments (gently rubbing in a to and from movement with a roughened piece of stainless-steel wire, covered tightly in cotton wool, along the intimae of aortic ring-generating less than 15% relaxation with acetylcholine).…”

“…Nitric oxide (NO) release was assessed by application of Griess reaction, as described previously ( Anwar et al, 2017 ). The manufacturer’s protocol was followed for measurement of total nitrate and nitrite content (NO x ; a measure of NO released) using a colorimetric assay kit (Cayman Chemical Company, Ann Arbor, MI, United States).…”

Formononetin induces vasorelaxation in rat thoracic aorta via regulation of the PI3K/PTEN/Akt signaling pathway

“…43 Stimulation of Akt enhances the activity of eNOS by phosphorylating serine at 1,177 and triggers the release of NO. 44 To test our hypothesis, we chose a 30 μM concentration for all subsequent experiments in accordance with the dose-dependent dilation of FMN. FMN augmented cellular NO production via eNOS phosphorylation, which is evident from the suppression of this effect by l -NAME.…”

Medicinal Plants as a Potential and Successful Treatment Option in the Context of Atherosclerosis

“…radix is a herbal formula suppress the expression of ICAM-1 and VCAM-1 and production of MCP-1 in TNF-a stimulated human umbilical vein endothelial cells (Koon et al, 2011). Sage also has antihypertensive activity as it was shown that sage extract increased nitric oxide production and relaxed endothelium-intact rings in experiments on isolated thoracic aorta from rats (Anwar et al, 2017).…”