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I Piper

Publications and source records attributed to I Piper.

30 records · Page 2Linked to original sources
PubMed1992

Cross tolerance between cromakalim and RP49356 in the uterus of the rat in vivo and in vitro.

We investigated tolerance to the potassium (K+) channel openers, cromakalim and RP49356 and cross tolerance between them in the uterus of the rat. Continuous infusion of RP49356 in vivo produced 5.2-fold (200 or 300 micrograms/kg per h) and 7.2-fold (600 micrograms/kg per h) desensitization of the uterus to RP49356. Uterine sensitivity to RP49356 was reduced 7.4-fold in cromakalim-tolerant rats and sensitivity to cromakalim was reduced 7.9-fold in RP49356-tolerant rats. Incubation of isolated uterus with 10 microM cromakalim for 4 h reduced uterine sensitivity to cromakalim by about 45-fold and to RP49356 by 2.1-fold but did not alter sensitivity to salbutamol. Incubation with 10 microM RP49356 for 4 h reduced sensitivity to RP49356 by 2.5-fold and to cromakalim by 3.8-fold. Occurrence of uterine tolerance to K+ channel openers in vitro suggests that tolerance in vivo has a pharmacodynamic basis. Cross tolerance between cromakalim and RP49356 provides evidence that these two K+ channel openers possess common binding sites and/or mechanism(s) of action. However, the greater extent of self-tolerance to cromakalim than to RP49356 suggests a difference in their actions.

Animals↗
PubMed1990

Effects of several potassium channel openers and glibenclamide on the uterus of the rat.

1. The ability of several potassium (K+) channel openers to inhibit spasm of the uterus of the nonpregnant rat and their susceptibility to antagonism by glibenclamide was assessed in vitro and in vivo. 2. In the isolated uterus exposed to oxytocin (0.2 nM), cromakalim, RP 49356 and pinacidil were of similar potency (mean pD2 = 6.4, 6.0 and 6.2 respectively) while minoxidil sulphate was of lower potency (pD2 = 4.7). Glibenclamide antagonized cromakalim and RP 49356 with the interactions consistent with competitive antagonism (mean pA2 of 6.57 and 7.00 respectively). Glibenclamide also antagonized pinacidil (pA2 = 6.22) but the slope of the Schild plot was significantly greater than -1. Neither salbutamol nor minoxidil sulphate was antagonized by glibenclamide (10 microM). 3. Cromakalim (1 and 10 microM), RP 49356 (1 and 10 microM), pinacidil (1 microM) and minoxidil sulphate (100 microM) suppressed spasm evoked by low (less than 40 mM) but not high (greater than or equal to 40 mM) KCl concentrations. Glibenclamide (10 microM) prevented cromakalim (10 microM)-, RP 49356 (10 microM)- and pinacidil (10 microM)-induced suppression of KCl (20 mM)-evoked spasm. Pinacidil (10 and 100 microM), cromakalim (100 microM) and salbutamol (0.01-1 microM) inhibited spasm evoked by all concentrations of KCl (10-80 mM). Suppression of spasm evoked by KCl (10-80 mM) by cromakalim (100 microM) and pinacidil (100 microM) was insensitive to glibenclamide (10 microM). 4. Cromakalim (0.1 mg kg-1) and RP 49356 (0.1 mg kg-1), given by i.v. bolus injection, inhibited uterine contractions, produced a fall in blood pressure and a slight tachycardia in the conscious ovariectomized rat. Glibenclamide (20mgkg-'), given by i.v. infusion, antagonized the vascular and uterine smooth muscle relaxant properties of cromakalim and RP 49356. 5. Several K+ channel openers are uterine relaxants. The antagonism of cromakalim, RP 49356 and pinacidil, at low concentrations, by glibenclamide suggests their actions may involve an ATP-sensitive K+channel. High concentrations of pinacidil (10 and 100 microM) and cromakalim (100 microM) may exert an additional action in the uterus. The low potency of minoxidil sulphate and its insensitivity to glibenclamide in the isolated uterus suggests that its mechanism of action may differ from that of the other K+ channel openers.

Animals↗
PubMed1989

A study of the muscarinic receptor subtype mediating mucus secretion in the cat trachea in vitro.

Mucus secretion from the cat trachea simulated by muscarinic receptor agonists has been studied by monitoring both the weight and acid glycoconjugate content of samples taken from an in vitro preparation. The nature of the receptor has been probed using a number of competitive muscarinic receptor antagonists by estimating their affinities from the degree to which the response could be blocked. Antagonist affinities have also been compared with those obtained in tracheal smooth muscle and atria from the guinea-pig. Atropine had similar affinities for all receptors investigated. 4DAMP and AF-DX116 had relatively high (pA2 = 9) and low (pA2 = 6) affinities respectively for the secretory receptor. The pA2 value of 7.5 calculated for pirenzepine suggested that the receptor was not of the M1 subtype. However, the value was higher than that for pirenzepine in both guinea-pig tissues indicating that the receptor may be an 'intermediate' between M1 and M2 subtypes. The lack of antagonists with absolute selectivity for a particular subtype of the muscarinic receptor prohibits a definitive classification.

Animals↗
PubMed1989

Improvement in post-traumatic spinal cord blood flow with a combination of a calcium channel blocker and a vasopressor.

We have recently shown that nimodipine, a calcium channel blocker, can increase spinal cord blood flow (SCBF) in normal rats and can improve SCBF after spinal cord trauma if the mean systemic arterial pressure (mSAP) is restored to normal levels by the vasopressor, adrenalin. The present study is a further analysis of the improvement in post-traumatic SCBF (measured with the hydrogen clearance technique) with the combination of adrenalin and nimodipine. In addition, image analysis was used to study the potential risk of this combination for exacerbating intramedullary hemorrhage in the injured spinal cord. SCBF, mSAP, and other physiologic parameters were measured preinjury, postinjury, and post-treatment. A 53.0-gram clip compression injury at the T1 spinal segment was delivered for 1 minute to three treatment groups (saline, adrenalin, and adrenalin plus nimodipine) comprised of five rats each. Injury caused a marked decline in SCBF and mSAP. Treatment with adrenalin alone or combined with nimodipine (1.5 micrograms/kg/min IV) improved mSAP to 100-125 mm Hg. However, adrenalin alone failed to improve SCBF, whereas nimodipine plus adrenalin produced a marked improvement of approximately 60% in post-traumatic SCBF. Morphometric analysis showed no significant difference between per cent area or volume of hemorrhage between the three treatment groups, although there was a trend for increased hemorrhage in the adrenalin-alone group perhaps due to the higher post-traumatic mSAP in this group. Further studies are required to find the minimal elevation in mSAP produced by a vasopressor that would still cause an improvement in post-traumatic SCBF by nimodipine, and to determine whether this combination improves function after spinal cord injury.

Animals↗
PubMed1987

A microcomputer system for on-line collection of blood flow and related physiological data.

A multi-disciplinary approach is described for the development of a microcomputer based on-line data collection system for blood flow experiments. Well designed software provides a flexible approach to data collection, which is particularly suited to blood flow research laboratories. The choice of well supported hardware ensures ease of development with minimum time and cost.

Blood Circulation↗
PubMed1987

Decompression of the spinal cord improves recovery after acute experimental spinal cord compression injury.

The value of decompression after spinal cord injury in patients is still an unresolved issue. It has previously been shown in our laboratory that functional recovery in rats after cord compression varied with both the force and time until decompression. However, the longest duration studied was only 15 minutes, which is far less than that usually encountered in clinical practice, and therefore, the present study was undertaken to determine the value of decompression after more prolonged periods of compression. A factorially designed experiment with five rats per cell was used with the clip compression injury model. Forces of 2.3, 16.9 or 53.0 gms were applied at C7-T1 until decompression was performed after 15, 60, 120, or 240 minutes of compression. Functional recovery was assessed weekly for 8 weeks using the inclined plane technique. Maximum and minimum performance limits were established in normal rats and rats with cord transection, respectively. Univariate analysis and multiple comparison tests were used to analyse the data. The major determinant of recovery was the force of the injury. For example, the animals injured by the 2.3 gm clip performed significantly better than those injured at higher forces for all times until decompression (p less than 0.0001), and there was a significant difference in recovery between the groups injured by the 16.9 and 53.0 gm clips, although only for the 15 minutes until decompression group (p less than 0.05). The time until decompression also affected recovery, but only for the lighter compression forces (2.3 and 16.9 gm). For example, animals decompressed after 60 minutes of 2.3 gm compression recovered significantly better than those decompressed after 240 minutes (p less than 0.05). Thus, if the initial injury force is small, decompression is beneficial even after prolonged injury.

Animals↗
PubMed1987

Recovery of spinal cord function induced by direct current stimulation of the injured rat spinal cord.

Direct current stimulation has been shown by others to enhance the regeneration of several types of tissues, including nervous tissue in some species. The purpose of the present experiment was to assess the value of direct current stimulation for enhancing the recovery of spinal cord function after clip compression injury of the rat spinal cord. Twenty Wistar rats underwent a 1-minute, 50-g clip compression injury at T-1, after which electrodes were placed epidurally with the anode proximal and the cathode distal to the injury site. These electrodes were attached to a stimulator implanted subcutaneously. Ten animals received stimulators that produced a constant current of 14 microA, and the remainder received stimulators with no electrical output and served as controls. Assignment of stimulators was random, and the treatment group was not identified until sacrifice. Neurological function was tested weekly for 15 weeks by the inclined plane technique, after which the animals were killed and the injured cords were examined for histological evidence of regeneration. The mean inclined plane result for the treatment group (39 +/- 5 degrees) was significantly better than that for the control group (31 +/- 6 degrees) (P less than 0.02), although there was no significant difference in histological findings between the two groups. Thus, direct current stimulation of the injured mammalian spinal cord produced improvement in neurological function and warrants further investigation.

Animals↗
PubMed1987

Effect of a calcium channel blocker on posttraumatic spinal cord blood flow.

The normal rat spinal cord blood flow (SCBF) has been shown to increase after administration of nimodipine, a calcium channel blocker. The present study investigates the capability of nimodipine to improve SCBF, as measured by the hydrogen clearance technique, after a 53.0-gm clip compression injury to the T-1 segment of the rat spinal cord. The profound drop in mean systemic arterial blood pressure (MSAP) after cervical cord injury precluded any improvement in posttraumatic SCBF by nimodipine alone. Hence, in a randomized controlled study with five rats per group, pressor agents (whole blood, angiotensin, or adrenaline) were infused to maintain MSAP between 100 and 120 mm Hg after injury. Control animals received only a saline infusion. Nimodipine at the optimal dose found in normal animals (1.5 microgram/kg/min) was added to the pressor agents. The MSAP and other physiological parameters were measured in rats receiving the pressor agents only and in those receiving pressor agents combined with nimodipine. In rats receiving whole blood, angiotensin, or adrenaline the posttraumatic MSAP improved to between 100 and 120 mm Hg, but there was no improvement in SCBF compared to the saline group. The addition of nimodipine decreased MSAP and SCBF in all groups except those animals also receiving adrenaline, where the MSAP was maintained at 109 +/- 5 mm Hg. In these animals a significant increase in posttraumatic SCBF from 16.5 +/- 2.1 to 20.2 +/- 2.3 ml/100 gm/min (mean +/- standard error of the mean) occurred at the site of injury with the addition of nimodipine. The maintenance of an adequate MSAP by a pressor agent was crucial for nimodipine to improve posttraumatic SCBF by its ability to dilate the spinal vascular bed. Adrenaline was the only pressor agent that could fulfill the above criteria, although other pressor agents need to be investigated. Experiments are underway with the combination of adrenaline and nimodipine to further verify these encouraging results demonstrating an improvement in posttraumatic ischemia of the spinal cord.

Angiotensin II↗
PubMed1985

Increase in rat spinal cord blood flow with the calcium channel blocker, nimodipine.

Nimodipine, a calcium channel blocker, is known to increase cerebral blood flow. In the present study, the authors investigated the effect of nimodipine on spinal cord blood flow in normal rats. Cardiovascular parameters, including mean systemic arterial blood pressure, cardiac output, and heart rate, were recorded during infusion of nimodipine in a dose-response fashion. The experiment was a randomized blind study in which four groups of five rats received different doses of nimodipine (0.001, 0.01, 0.05, and 0.10 mg/kg) intravenously over 30 minutes, and a control group of five rats received only the diluent. The hydrogen clearance and thermodilution techniques were used to measure spinal cord blood flow and cardiac output, respectively. The 0.05-mg/kg dose of nimodipine caused the largest increase in spinal cord blood flow, with a 40% increase over the preinfusion level, although there was a 25% reduction in mean arterial pressure. The 0.10-mg/kg dose did not increase spinal cord blood flow more than the 0.05-mg/kg dose, most likely due to the concomitant 37% reduction in mean arterial pressure. Cardiac output was significantly increased by the 0.05- and 0.10-mg/kg doses secondary to the drop in total peripheral resistance. The increase in spinal cord blood flow produced by nimodipine lasted approximately 20 minutes after the termination of the infusion. Thus, nimodipine at a dose of 0.05 mg/kg markedly increased blood flow in the normal spinal cord even though there were major changes in mean systemic arterial pressure and cardiac output. Further research is required to determine whether this drug might be beneficial in treating ischemic states of the spinal cord, such as posttraumatic ischemia.

Analysis of Variance↗
PubMed1981

Effects of inhibiting prolactin secretion on the maintenance of embryonic diapause in the suckling rat.

Treatment of rats with bromocriptine between days 5 and 8 after the post-partum mating resulted in suppression of serum prolactin levels and caused luteal regression. Although this treatment led to embryonic resorption when suckling was prevented by removing litters soon after birth, the diapausing embryos of animals nursing a litter of eight pups were unaffected by the treatment. These results suggest that the high levels of prolactin and progesterone in the circulation during lactation are not responsible for maintenance of the diapausing state.

Animals↗