Pharmacological Justification for the Medicinal Use of Plumeria rubra Linn. in Cardiovascular Disorders

Plumeria rubra (L.) is a traditional folkloric medicinal herb used to treat cardiovascular disorders. The present investigation was methodically planned to investigate the pharmacological foundations for the therapeutic effectiveness of P. rubra in cardiovascular illnesses and its underlying mechanisms. Ex vivo vaso-relaxant effects of crude leaf extract of P. rubra were observed in rabbit aorta ring preparations. Hypotensive effects were measured using pressure and force transducers connected to the Power Lab data acquisition system. Furthermore, P. rubra displayed cardioprotective properties in rabbits when they were exposed to adrenaline-induced myocardial infarction. In comparison to the intoxicated group, the myocardial infarction model showed decreased troponin levels, CK-MB, LDH, ALT, ALP, AST, and CRP, as well as necrosis, apoptosis, oedema, and inflammatory cell enrollment. P. rubra has revealed good antioxidant properties and prolonged the noradrenaline intoxicated platelet adhesion. Its anticoagulant, vasorelaxant, and cardioprotective effects in both in vivo and ex vivo investigations are enabled by blocking L-type calcium channels, lowering adrenaline, induced oxidative stress, and tissue tear, justifying its therapeutic utility in cardiovascular disorders.

Experimental Setting for Applying Mechanical Stimuli to Study the Endothelial Response of Ex Vivo Vessels under Realistic Pathophysiological Environments

This paper describes the design, construction and testing of an experimental setting, making it possible to study the endothelium under different pathophysiological conditions. This novel experimental approach allows the application of the following stimuli to an ex vivo vessel in a physiological bath: (a) a realistic intravascular pressure waveform defined by the user; (b) shear stress in the endothelial layer since, in addition to the pressure waveform, the flow through the vessel can be independently controlled by the user; (c) conditions of hypo/hyperoxia and hypo/hypercapnia in an intravascular circulating medium. These stimuli can be applied alone or in different combinations to study possible synergistic or antagonistic effects. The setting performance is illustrated by a proof of concept in an ex vivo rabbit aorta. The experimental setting is easy to build by using very low-cost materials widely available. Online Supplement files provide all the technical information (e.g., circuits, codes, 3D printer drivers) following an open-source hardware approach for free replication.

In vitro and in vivo biological approach to validate folkloric claims of Trianthema triquetra Rottler & Willd

Trianthema triquetra Rottler & Willd (Tt.Cr) is used in traditional practices as a remedy for various ailments. Hence current research was commenced to authenticate the folkloric uses. To discover spasmolytic potential, Tt.Cr was applied to isolate jejunum, while isolated tracheal and aorta tissues were used to determine the tissue relaxing properties of the extract. Anti-lipoxygenase activity was determined in vitro using Baicalein as standard. In vivo testing was carried to examine the potentiality of the herb to treat pyrexia and pain. Tt.Cr showed dose-dependent (0.01 - 3.0 mg/ml) spasmolytic effects in jejunum tissues and relaxed K+ (80 mM)-induced spasm and triggered rightwards shift of Ca+2 concentration-response curves. Carbachol (1μM)- together with K+ (80 mM) - induced tracheal spasm was also relaxed by Tt.Cr (0.01 to 1.0 mg/ml). Additionally, Tt.Cr (0.01 - 1.0 mg/ml) relaxed phenylephrine (1 μM) and K+ (80 mM) - treated constricted rabbit aorta. Tt.Cr (0.5 mM) inhibited lipoxygenase enzyme. Tt.Cr (80 mg/kg) settled pyrexia in rabbits comparable to aspirin and prolonged tail deflection time in mice (100 mg/kg) hence proving analgesic activity. The Tt.Cr demonstrated antispasmodic, bronchodilation and vasodilation properties probably by blocking calcium channels. These outcomes generate logic behind ancient application of herb for numerous ailments such as asthma, cough, heart problems and spasm.

Increased receptor expression supports vascular reactivity of the rabbit aorta during preservation

OBJECTIVES The mechanistic understanding of vascular functional impairment during preservation time helps determine the optimal time frame in which explanted arteries can be used. The method of choice is to measure vascular reactivity and receptor expression. Our goal was to study the influence of preservation for 24 and 48 h on vascular reactivity and receptor expression in rabbit aorta. METHODS Aortic rings preserved in Krebs–Henseleit solution were evaluated fresh (t0), 24 h (t24) and 48 h (t48) after harvest for (i) vascular reactivity as sensitivity (pD2) and maximum effect in response to potassium chloride, U46619 (thromboxane-A2 agonist), phenylephrine, carbachol and isoproterenol, in an organ bath; and for (ii) expression of α1, β2 and thromboxane-prostanoid receptors, by immunofluorescence. RESULTS Compared to the control, after 24 h of preservation, potassium chloride-induced pD2 increased a significant 3.6%, whereas U46619-induced vasoconstriction decreased 9%. None of the agonists affected vasodilation. Intimal and medial α1 receptor expression increased 2.5-fold. After 48 h of preservation, α1 expression and vasoconstrictor responses remained similar to those after 24 h of preservation, but in vasodilation the carbachol-induced maximum effect decreased 30% whereas isoproterenol-induced pD2 increased 4% and the maximum effect increased 10%. TP and β2 expression in the intima and media increased 1.8- and 2.5-fold, respectively. CONCLUSIONS Up to 48 h of preservation, the adrenergic pathway and its receptors support vasoconstriction and vasodilation, despite a significant deterioration in the prostanoid pathway.

Estimating Arterial Cyclic Strain from the Spacing of Endothelial Nuclei

Background The non-uniform distribution of atherosclerosis within the arterial system is widely attributed to variation in haemodynamic wall shear stress. It may also depend on variation in pressure-induced stresses and strains within the arterial wall; these have been less widely investigated, at least in part because of a lack of suitable techniques. Objectives Here we show that local arterial strain can be determined from impressions left by endothelial cells on the surface of vascular corrosion casts made at different pressures, even though only one pressure can be examined in each vessel. The pattern of pits in the cast caused by protruding endothelial nuclei was subject to “retro-deformation” to identify the pattern that would have occurred in the absence of applied stresses. Methods Retaining the nearest-neighbour pairs found under this condition, changes in nearest-neighbour vectors were calculated for the pattern seen in the cast, and the ratio of mean changes at different pressures determined. This approach removes errors in simple nearest-neighbour analyses caused by the nearest neighbour changing as deformation occurs. Results The accuracy, precision and robustness of the approach were validated using simulations. The method was implemented using confocal microscopy of casts of the rabbit aorta made at systolic and diastolic pressures; results agreed well with the ratio of the macroscopic dimensions of the casts. Conclusions Applying the new technique to areas around arterial branches could support or refute the hypothesis that the development of atherosclerosis is influenced by mural strain, and the method may be applicable to other tissues.