Pengaruh diabetes ke atas tekanan darah, kadar jantung dan aktiviti saraf simpatetik renal dalam tikus normal dan hipertensif

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Date
2002-04
Authors
Arifin, Helmi
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Abstract
This study examines the effect of diabetes on the blood pressure, heart rate and renal sympathetic nerve activity in the presence and absence of rilmenidine and volume expansion in normal and hypertensive rats. Male Sprague-Dawley (SD) and Spontaneously Hypertensive Rats (SHR.) were used. Diabetes was chemically induced using streptozotocin (STZ) 60 mglkg intraperitoneally and the acute study was carried out seven days later. Body weight, total water intake, total urine output, urine sodium excretion were determined every 24 hours. The blood glucose \Vas measured first before acute study was commenced. The animals were anaesthetised by a mixture of fluothane/02 with flow rate 4 and 5 1/min for 2 min and thereafter maintained on chloralose/urethane (12 mg and 180 mg/ml) 0.1 ml/5 min (6-7 times) followed by 0.05 ml/30 min respectively, administered intravenously via femoral vein. Blood pressure (systolic and diastolic) and heart rate were monitored using a Grass transducer connected to Lab VIEW data acquisition system on a Macintosh computer. Renal nerves were isolated and placed on bipolar electrodes and their activity measured using the above system. Following the collection of baseline data, bolus doses of rilmenidine, 0, 100, 300 and 1000 Jlg/kg body weight were administered for rilmenidine treatment. For volume expansion treatment, saline infusion was increased such that the animal received 0.25% body weight/min for over 40 min. Changes in blood pressure, heart rate and renal sympathetic nerve activity were recorded. The effects of rilmenidine on blood pressure, heart rate and renal sympathetic nerv·e activity during volume expansion \vere examined using various rilmenidine doses before the actual volume expansion process begin. The results showed that blood pressure was increased in diabetic state in SD rats and reduced in SHR. rats. Heart rate (HR.) were decreased at doses of 300 !J.g/kg and I 000 !J.g/kg of rilmenidine, except in SHR. rats only at a high dose ( 1000 j..t.g/kg). ~lean while renal sympathetic nerve activity (RSNA) was increased in diabetic state in SD rats while no c~anges were observed in SHR. rats. Reductions in systolic blood pressure (SBP) \Vere observed in all groups of the rats at all doses of · rilmenidine administered. The diastolic blood pressure (DBP) were reduced at doses of 300 ~tg/kg and l 000 !lg/kg of rilmenidine, except in the SHR. group where these reductions were seen at all doses. The reduction of blood pressure in diabetic rats was significantly smaller than non diabetic rats. No meaningful changes in HR. were observed in non-diabetic rats at all doses of rilmenidine while in diabetic rats, decrease in HR. were observed at rilmenidine doses of 300 !J.g/kg and 1000 j..t.g/kg. In SD rats , a reduction in RSNA was seen at all the doses of rilmenidine given whereas in SHR. rats reduction in RSNA were observed only at doses 300 !J.g/kg and 1000 j..t.g/kg. However in both of the diabetic rats (SDDIA and SHR.DIA), rilmenidine caused significant reduction in RSNA only at a high dose ( 1000 !J.g/kg). In volume expanded study, there were no meaningful changes in the systolic blood pressure in all groups of animal, but in SD rats SBP a reduction was observed. However, no significant changes in heart rate (HR.) (P>O.l) were observed throughout the volume expansion process. Futhermore, a significant reduction in RSNA was observed in all groups, but the reduction was clearly smaller in diabetic state compared to non diabetic state. Rilmenidine in volume expanded rats caused a reduction in the lowering blood pressure, heart rate and renal sympathetic nerve activity as compared to that observed in volume expanded animals without rilmenidine. More over this inhibition was greater in the diabetic state. Collectively, the data obtained indicate that in diabetes, the central drive generating renal sympathetic activity is resistant to regulation by neural pathways which involve the rilmenidine sensitive receptors, possibly the putative imidazoline receptor Cit).
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Keywords
Tekanan darah, kadar jantung , Aktiviti saraf simpatetik , Tikus normal
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