Effect of moxonidine versus clonidine and lisinopril on blood pressure and expression of renin gene in two kidney/one clip [2K/1 C] hypertensive rats

It has been suggested that imidazoline receptors rather than alpha-2 adrenoceptors are implicated in the sympathoinhibitory action of centrally acting antihypertensive drugs. I[1] Imdazoline receptors [I[1]Rs] are important for regulation of sympathetic drive. They are concentrated in the rostral ventrolateral medulla [RVLM], a part of the brainstem vasomotor center. The control of arterial blood pressure is mainly regulated via the sympathetic and angiotensin/ aldosterone cascades. The purpose of the present study was focused to assess the effect of oral administration and abrupt withdrawal of moxonidine versus clonidine and lisinopril on systolic pressure, to investigate the role of moxonidine versus clonidine and lisinopril on plasma noradrenaline level and plasma renin activity and to determine the genometric effect of moxonidine versus clonidine and lisinopril oral administration on renin gene expression in 2K1C renovascular hypertensive rats. Rats were made hypertensive with a clip on the left renal artery. The operation was conducted under light ether anesthesia. Three weeks after renal clipping. 2 series of experiments on male rats were conducted to evaluate the effect of the test drugs on the following parameters. 1- Effect of oral administration of the test drugs for a period of three weeks on the systolic pressure in 2K1C hypertensive rats measured via indirect rat-tail method. 2-Biochemical tests to estimate plasma norepiphrine level and plasma renin activity. 3- Renin gene expression measured by quantified RT-PCR. All test drugs elicited a remarkable significant reduction in systolic pressure of renovascular hypertensive rats. Discontinued administration of moxonidine did not trigger rebound hypertension observed with clonidine. These findings suggest that both imidazoline receptors and alpha 2- adrenoceptors are involved in the central antihypertensive effect of moxonidine, but that activation of imidazoline receptors is more important for its renal sympathinhibitory action. Additionally imidazoline derivatives and ACEIs are very effective agents for treatment of renovascular hypertension. The antihypertensive effect of moxonidine was accompanied by decrease in plasma norepinephrine, renin levels and renin gene expression in the renal tissue. Whereas lisinopril decreased plasma norepinephrine level but increased plasma renin activity in parallel with renin gene expression compared to the untreated 2K1C hypertensive control. The data presented in this report indicate that moxonidine is an orally effective antiypertensive agent in 2KIC hypertensive rats without an accompanying rebound hypertension on abrupt dicontinuation of the drug, which makes it advantageous over clonidine. Moxonidine therefore allies antihypertensive efficacy with excellent tolerance without triggering central side-effects as moxonidine selectively binds at therapeutic doses to I[1] imidazoline receptors. ACEI, lisinopril produced a significantly pronounced reduction in systolic pressure in 2K1C hypertensive rats. Lisinopril may be of greater benefit in management of renovascular hypertension. In light of these findings moxonidine represents a unique profile among centrally acting antihypertensive agents. Moxonidine offers an advantageous hemodynamic activity over clonidine and lisinopril and probably it exerts its strong antihypertensive effect through its affinity for I[1] imidazoline receptors rather than alpha[2] adrenergic receptors

Emergence agitation after sevoflurane anesthesia in children: prophylactic effect of clonidine versus two doses of fentanyl

Sevoflurane anesthesia in preschool children has been associated with an increased incidence of emergence agitation. Many factors may be incriminated in this phenomenon, but most important of them [other than anesthetic technique] is postoperative pain. We designed a study that included a non-surgical procedure in order to eliminate pain and we compared the effects of different drugs to attenuate this anesthesia related complication. Eighty children undergoing examination under anesthesia between the ages of 18 months and 6 years were randomly assigned to receive fentanyl lug/kg, fentanyl 2 ug/kg, clonidine 2 ug/kg or placebo after receiving sevoflurane anesthesia. Blood samples were collected before discharge from the PACU to evaluate the hormonal part of stress response associated with agitation. The children's behavior was assessed with a special agitation scale in the PACU and total hospital discharge time was measured. Clonidine 2ug/kg and fentanyl lug/ kg were found to decrease much the incidence of postoperative agitation without increasing discharge time, vomiting or itching among preschool children exposed to sevoflurane anesthesia in nonpainful procedures

comparison of clonidine, tramadol and meperidine in post epidural anaesthetic shivering in parturients

This study was performed to compare the antishivering effects and accompanying side effects among clonidine, tramadol and meperidine in parturients. Sixty parturients who shivered during casarean delivery under epidural anaesthesia and requested to one of three groups for IV treatment group C [n=20] received clonidine 3 mirco g/kg Group T [n=20] received tramadol 0.5 mg /kg. and group M [n=20] received meperidine 0.5 mg /kg. the response rate[shivering ceased after treatment was 85%, 90% and 95% for groups C, T and M respectively. The time that elapsed from treatment to the time shivering ceased was 5.2 +/- 2.6 min, 4.1 +/- 1.6 min and 3.8 +/- 3.2 min for groups C, T and M respectively, no significant differences were shown for pruritus, nausea, vomiting or Apgar scores of new borns. We concluded that both tramadol and meperidine show faster response rate in the treatment of post epidural anaesthetic shivering when compared with clonidine

Effect of moxonidine versus clonidine on stress induced gastric ulceration in rats

The present study was conducted to evaluate the effect of moxonidine a selective I imidazoline receptor agonist and antihypertensive agent versus clonidine on experimental gastric ulceration in rats. The animals were divided into 5 groups [10 animals each]. One served as control [stress ulcer induced] and received no medication. Two groups were pretreated intraperitoneally for 21 consecutive days with moxonidine [0.01 and 1 ing/kg b.w] respectively. The other 2 groups were pretreated intraperitoneally for 21 consecutive days with clonidine [0.01 and 1 mg/ kg b.w] respectively. Gastric ulceration in rats were induced by using restraint or immobilization technique. The animals were left for 24 hours and then the stomach was cut and examined for lesions to detect gastric ulceration. The effect of two doses of moxonidine and clonidine were tested on stress induced ulcer. Also, the effect of efaroxan [selective I - imidazoline receptor blocker] and yohimbine [selective a blacker] on the gastroprolective effect of moxonidine and clonidine were assessed respectively. The results of the present study revealed that stress ulcer incidence, severity and number per stomach were all higher in control group. Moxonidine [0.01 and 1 mg/kg] was found to exhibit a more pronounced gastroprotective effect on stress induced gastric ulcer compared to a- agonist clonidine <0.01 mg/ kg] with reduction of ulcer index by 59.5 and 79.6% for two doses of moxonidine respectively and 40.13% for clonidine in comparison to control group. However clonidine Img/kg decreased ulcer index by only 3.28%. The gastroprotective effect of moxonidine and low dose of clonidine were abolished following pretreatment with efaroxan and yohimbine respectively In conclusion, the results of the present study indicate that moxonidine exhibits a more pronounced gastroprotective effect compared to low dose of clonidine. In addition, the effects of clonidine on gastric function is dose dependent with no gastroprotective effect at higher doses. So, moxonidine may be considered a better alternative to clonidine as an anti-hypertensive in patients with gastrointestinal disorders