Effect of pioglitazone on vasopressor responses to adrenergic agonists and angiotensin II in diabetic and non-diabetic spontaneously hypertensive rats

Pioglitazone, peroxisome proliferator-activated receptor [PPAR-gamma] agonist, is a therapeutic drug for diabetes. Present study investigated the interaction between PPAR-gamma and alpha adrenoceptors in modulating vasopressor responses to Angiotensin II [Ang II] and adrenergic agonists, in diabetic and non-diabetic Spontaneously Hypertensive Rats [SHRs]. Diabetes was induced with an i.p injection of streptozotocin [40 mg/kg] in two groups [STZ-CON, STZ-PIO], whereas two groups remained non diabetic [ND-CO, ND-PIO]. One diabetic and non-diabetic group received Pioglitazone [10mg/kg] orally for 21 days. On day 28, the animals were anaesthetized with sodium pentobarbitone [60mg/kg] and prepared for measurement of systemic haemodynamics. Basal mean arterial pressure of STZ-CON was higher than NDCON, whereas following pioglitazone treatment, MAP was lower compared to respective controls. MAP responses to i.v administration of NA, PE, ME and ANG II were significantly lower in diabetic SHRs: STZ-CON vs. ND-CON [35%]. Pioglitazone significantly decreased responses to NA, PE, ME and ANG II in ND-PIO versus ND-CON by 63%. Responses to NA and ANG II were significantly attenuated in STZ-PIO vs. ND-PIO [40%]. PPAR-gamma regulates systemic hemodynamic in diabetic model and cross-talk relationship exists between PPAR-gamma and alpha1-adrenoceptors, ANG II in systemic vasculature of SHRs

effect of high-fructose intake on the vasopressor response to angiotensin ii and adrenergic agonists in Sprague-Dawley rats

Effect of losartan was assessed on systemic haemodynamic responses to angiotensin II [Ang II] and adrenergic agonists in the model of high-fructose-fed rat. Twenty-four Sprague-Dawley [SD] rats were fed for 8 weeks either 20% fructose solution [FFR] or tap water [C] ad libitum. FFR or C group received losartan [10mg/kg/day p.o.] for 1 week at the end of feeding period [FFR-L and L] respectively, then the vasopressor responses to Ang II, noradrenaline [NA], phenylephrine [PE] and methoxamine [ME] were determined. The responses [%] to NA, PE, ME and Ang II in FFR were lower [p<0.05] than C [FFR vs. C; 22 +/- 2 vs. 32 +/- 2, 30 +/- 3 vs. 40 +/- 3, 9 +/- 1 vs. 13 +/- 1, 10 +/- 1 vs. 17 +/- 1] respectively. L group had blunted [p<0.05] responses to NA, PE, ME and Ang II compared to C [L vs. C; 26 +/- 2 vs. 32 +/- 2, 30 +/- 3 vs. 40 +/- 3, 7 +/- 0.7 vs. 13 +/- 1, 5 +/- 0.4 vs. 17 +/- 1] respectively. FFR-L group had aggravated [p<0.05] response to NA and ME, but blunted response to Ang II compared to FFR [FFR-L vs. FFR; 39 +/- 3 vs. 22 +/- 2, 11 +/- 1 vs. 9 +/- 1, 3 +/- 0.4 vs. 10 +/- 1] respectively. Fructose intake for 8 weeks results in smaller vasopressor response to adrenergic agonists and Ang II. Data also demonstrated an important role played by Ang II in the control of systemic haemodynamics in FFR and point to its interaction with adrenergic neurotransmission

Carbopol 934, 940 and Ultrez 10 as viscosity modifiers of palm olein esters based nano-scaled emulsion containing ibuprofen

Micro-emulsions and sometimes nano-emulsions are well known candidates to deliver drugs locally. However, the poor rheological properties are marginally affecting their acceptance pharmaceutically. This work aimed to modify the poor flow properties of a nano-scaled emulsion comprising palm olein esters as the oil phase and ibuprofen as the active ingredient for topical delivery. Three Carbopol resins: 934, 940 and Ultrez 10, were utilized in various concentrations to achieve these goals. Moreover, phosphate buffer and triethanolamine solutions pH 7.4 were used as neutralizing agents to assess their effects on the gel-forming and swelling properties of Carbopol 940. The addition of these polymers caused the produced nano-scaled emulsion to show a dramatic droplets enlargement of the dispersed globules, increased intrinsic viscosity, consistent zeta potential and transparent-to-opaque change in appearance. These changes were relatively influenced by the type and the concentration of the resin used. Carbopol 940 and triethanolamine appeared to be superior in achieving the proposed tasks compared to other materials. The higher the pH of triethanolamine solution, the stronger the flow-modifying properties of Carbopol 940. Transmission electron microscopy confirmed the formation of a well-arranged gel network of Carbopol 940, which was the major cause for all realized changes. Later in vitro permeation studies showed a significant decrease in the drug penetration, thus further modification using 10% w/w menthol or limonene as permeation promoters was performed. This resulted in in vitro and in vivo pharmacodynamics properties that are comparably higher than the reference chosen for this study

Study of surface activity of piroxicam at the interface of palm oil esters and various aqueous phases

The surface activity of some non-steroidal anti-inflammatory agents like ibuprofen was investigated extensively. This fact has attracted the researchers to extend this behavior to other agents like piroxicam. Piroxicam molecules are expected to orient at the interface of oil and aqueous phase. The aim of this study was, firstly, to assess the surface and interfacial tension behaviour of newly synthesised palm oil esters and various pH phosphate buffers. Furthermore, the surface and interfacial tension activity of piroxicam was studied. All the measurements of surface and interfacial tension were made using the tensiometer. The study revealed that piroxicam has no effect on surface tension values of all pH phosphate buffers and palm oil esters. Similarly, various concentrations of piroxicam did not affect the interfacial tensions between the oil phase and the buffer phases. Accordingly, the interfacial tension values of all mixtures of oil and phosphate buffers were considerably high which indicates the immiscibility. It could be concluded that piroxicam has no surface activity. Additionally, there is no surface pressure activity of piroxicam at the interface of palm oil esters and phosphate buffers in the presence of Tweens and Spans