Effect of repeated administration of some non-steroidal anti-inflammatory drugs on some hepatorenal parameters in the rabbit

Thirty rabbits were included in this study to determine and compare the compare the possible effects of repeated oral daily administration for four weeks of four non-steroidal anti-inflammatory drugs [NSAIDs] belonging to different structural groups on some hepatorenal parameters. These drugs included; tiaprofenic acid [20 mg/kg], piroxicam [10 mg/kg], Naproxen [10 mg/kg] and diclofenac [10 mg/kg]. The following parameters were studied; liver function tests [serum alanine aminotransferase ALT, serum aspartate aminotransferase AST alkaline phosphatase total bilirubin, total proteins and albumin], and markers for renal function [blood urea, serum creatinine, sodium and potassium]. The results indicated that naproxen and diclofenac induced significant increases in serum ALT, AST, alkaline phosphatase, total bilirubin blood urea and serum creatinine with significant decrease of total serum proteins and albumin. On the other hand tiaprofenic acid and piroxicam did not induce any significant change in the studied parameters. The results indicated that tiaprofenic acid and piroxicam may be safer NSAIDs to be used for long term therapy especially in patients who may suffer from hepatorenal troubles

Role of central cholinergic drugs in combating haemorrhagic shock

Haemorrhagic shock was induced in rats by intermittent bleeding until the mean arterial blood pressure fell and stabilized at about 30 mmHg. After induction of haemorrhagic shock rats were subdivided into 5 groups. The first group [control] of rats were given saline [1 ml/Kg I.V.], all rats died within 20 minutes. The second group of rats were given physostigmine [17.5 35 and 70 micro g/Kg I.V.], all rats survived up to 90 minutes, with dose dependent increase in the mean arterial blood pressure from 32 mmHg after haemorrhagic shock to 90 mmHg after treatment with 70 ug/kg I.V. physostigmine. In the third group neostigmine failed to produce such a pressor effect since there was non-significant rise in the mean arterial pressure. In the fourth group atropine sulphate pretreatment [2 mg/kg I.V.], failed to prevent the pressor effect of physostigmine. In the fifth group guanethidine pretreatment prevented the pressor effect of physostigmine. It is concluded from this study that central cholinomimetics can combat hypovolaemic shock through central activation of peripheral sympathetic mechanism, which results in rise of blood pressure together with mobilization and redistribution of residual blood from peripheral pooling

Effect of ramipril [HOE 498] on presynaptic nerve transmission in the isolated rabbits heart

The role of the angiotensin converting enzyme inhibitor [ACEI], HOE 498 [ramipril] in affecting the presynaptic function in the isolated perfused rabbit's heart was studied. Norepinephrine [NE] injected into the perfusate result in 17.3% rise in heart rate [HR], 34.96% increase in amplitude of contraction [AC] and 33.17% decrease in coronary flow [CF]. Following oral pretreatment of the rabbits with ramipril [1 mg/kg], significant decrease of NE effects on AC [41.9%] and CF [39.3%] was observed; whereas, HR did not change significantly. The presence of imipramine [4.7 muM] in the perfusate augmented the induced effect of NE on the HR [28.6%] and AC [51.3%], as well as CF [17.3%]. When imipramine was infused in the above-mentioned concentration in ramipril pretreated animals, there was a reduction in the NE-induced effects on HR [34.6%], AC [57.9%], as well as definite decrease in CF. Collectively, this data provides evidence for a presynaptic effect of ramipril on the rabbit's heart

Mechanism of arachidonic acid induced vasodilatation in the intact rat intestine

The dose dependency and mechanism of arachidonic acid [AA]-induced change of total superior mesenteric blood flow [MBF] was investigated in anaesthetized albino rats. MBF of the intact autoperfused mesentery was measured with an extracorporeal electromagnetic flow probe. Direct measurements of systemic blood pressure [BP] were also determined. Intramesenteric arterial [IMA] bolus injections of 10-40 ug of AA caused dose-dependent vasodilatation and decrease in mesenteric vascular resistance [MVR]. Mesenteric vascular responses to AA were abolished by indomethacin 5 mg/kg I.V. The preparation was capable of active dilatation when challenged with acetyl choline [ACh] and of active constriction when angiotensin II [A II] was injected. Prostaglandin I2, [PGI 2], PGE 2 and PGD 2 caused mesenteric vasodilatation, whereas PGF 2gamma caused mesenteric vasoconstriction. These results indicate that cyclooxygenase derived product [S] are responsible for the mesenteric vasodilator effect of AA in the intact rat mesenteric preparation

Alteration of blood pressure response to arachidonic acid in diabetic rats

The dose dependency and mechanism of arachidonic acid [AA]-induced decrement in systemic blood pressure [BP] was investigated in diabetic rats, versus their controls: Intravenous [I.V.] injection of 0.5-2 mg AA into diabetic rats [2 weeks after a single S.C. injection of alloxan, 175 mg/kg] caused dose dependent decrement in BP. The diabetic rats displayed decreased responsiveness to the hypotensive effect of AA compared to control rats. AA hypotensive responses were completely abolished by indomethacin [5 mg/kg I.V.]. Prostaglandin F2gamma [PGF2gamma], 20 ug, and norepinephrine [NE], 4 ug, increased BP whereas acetyloholine [ACh], 2 ug, lowered it in both diabetic and control rats. No significant differences were detected for the effects of the above mentioned drugs between the two groups. The findings indicate that AA is converted into cyclo-oxygenase derived products with predilection to formation of excess vasoconstrictor[s] metabolites and/or depressed vasodilator[s] production