Class differences in the effects of calcium channel blockers in the rat remnant kidney model.
(17/1487)
BACKGROUND: Controversy persists as to the existence of class differences between calcium channel blockers (CCBs) in their ability to provide renoprotection and as to potential mechanisms involved. METHODS: Rats with 5/6 renal ablation were left untreated or received diltiazem, verapamil, or felodipine after the first week, and the relationship between continuous radiotelemetrically measured blood pressure (BP) and glomerulosclerosis (GS) was assessed at seven weeks. Additionally, the effects of these CCBs on renal autoregulation and hypertrophy were examined at three weeks after renal ablation. RESULTS: Although an excellent linear correlation was observed between the average BP levels and GS in all groups (r = 0.75 to 0.84, P < 0.01), significant protection was not achieved with any of the CCBs, but for different reasons. The antihypertensive effects of diltiazem were not sustained beyond the second week. Verapamil significantly reduced the average BP (144 +/- 4 mm Hg vs. 181 +/- 8 in untreated rats) but shifted the slope of the relationship between BP and GS (increase in percentage GS/mm Hg increase in average systolic BP) to the left (x intercept 121 vs. 144 mm Hg for untreated rats, P < 0.01) so that GS was not reduced. Felodipine also significantly reduced the average BP (144 +/- 3 mm Hg) and shifted the slope to the left (x intercept 123 mm Hg), but additionally made the slope steeper (2.3 +/- 0.5 vs. 0.82 +/- 0.2 in untreated rats). Because of these differing effects on the relationship between BP and GS, the rank order of GS for any given BP elevation was as follows: felodipine > verapamil > diltiazem = untreated. Felodipine, but not verapamil or diltiazem, caused additional impairment of the already impaired renal autoregulation in untreated rats, thereby explaining its adverse effects on GS. By contrast, the adverse effects of verapamil on GS were attributable to the greater amplitude of BP fluctuations that was observed in the verapamil-treated rats such that for any given average BP, these rats were exposed to greater peak pressures as compared with the other groups. None of the CCBs had a significant effect on glomerular hypertrophy. CONCLUSIONS: These class differences between CCBs in their relative impact on systemic BP profiles, renal autoregulation, and glomerular pressure transmission may have clinically significant implications and may account for the variable glomeruloprotection that has been observed with these agents in both experimental models and in humans. (+info)
Thermal dehydration-induced thirst in spontaneously hypertensive rats.
(18/1487)
Spontaneously hypertensive (SH) rats and normotensive Wistar-Kyoto (WKY) rats were exposed to either 25 or 37.5 degrees C for 3.5 h, and their thermal and water balance responses were compared. After exposure, either a blood sample was obtained or the rats were allowed to rehydrate for 4 h. SH rats had both higher core temperatures and evaporative water losses during heat exposure. Measurements of hematocrit, hemoglobin concentration, plasma protein and sodium concentrations, and plasma osmolality indirectly showed that the SH rats were dehydrated relative to the WKY rats after exposure to either 25 or 37.5 degrees C. SH rats drank significantly more water but also had significantly higher urine volumes than the WKY rats and thus rehydrated only slightly better than the WKY rats. SH and WKY rats had similar levels of water intake and urine output after 24 h of water deprivation. The elevated thermal response of SH rats to heat exposure does not appear to lead to uncompensatable changes in body water status. (+info)
Abated cardiovascular responses to chronic oral lisinopril treatment in conscious elderly rats.
(19/1487)
To determine whether the cardiovascular effects of chronic treatment with lisinopril are age related, we compared baroreflex sensitivity and pressor responsiveness in 4-mo- and 21-mo-old male rats that had been given oral lisinopril daily for 4 wk. Reflex bradycardia elicited by elevating blood pressure with phenylephrine was stronger in 4-mo-old rats than it was in 21-mo-old rats and also stronger in lisinopril-treated rats than it was in untreated rats of the same age. Pressor responses to angiotensin or norepinephrine were recorded after combined cholinergic and beta-adrenergic blockade and then analyzed not only as absolute but also as percent increases in mean pressure. Although pressor responses seemed to be slightly reduced by lisinopril when expressed as absolute increases in mean pressure, corresponding percent increases were always larger in 4-mo-old rats than they were in 21-mo-old rats and were clearly enhanced by lisinopril more in younger rats. The stronger overall enhancement of pressor responsiveness and reflex bradycardia in younger rats suggests that the cardiovascular effects of lisinopril diminish with advancing age. (+info)
Effects of feeding frequency and voluntary salt intake on fluid and electrolyte regulation in athletic horses.
(20/1487)
The effect of feeding frequency and voluntary sodium intake (VSI) on fluid shifts and plasma aldosterone concentration (PAC) were studied at rest and after exercise in six athletic horses. The horses were fed twice a day (2TD) and six times a day (6TD) for 25 days for each protocol, according to a changeover design. VSI was measured by weighing each horse's salt block daily. Feeding 2TD or 6TD caused no major alterations in fluid shifts, but in the 2TD treatment there was a postprandial increase in plasma protein concentration and osmolality that lasted <1 h. PAC and VSI were not affected by feeding frequency. VSI ranged from 0 to 62 mg x kg body weight-1 x day-1 and caused significant alterations in PAC. At VSI <26 mg x kg body weight-1 x day-1, a diurnal rhythm for PAC was noted. Water intake, fecal concentrations of sodium and potassium, and packed cell volume during exercise were influenced by VSI. The response to exercise did not differ between treatments. In conclusion, VSI, but not feeding frequency, has significant effects on fluid and electrolyte regulation in athletic horses. (+info)
Daily intake of copper from drinking water among young children in Sweden.
(21/1487)
Copper is an essential trace element that may cause intoxication if intake becomes excessive. Young children are at risk of intoxication because of high consumption of drinking water and immature copper metabolism. The aims of this prospective study were to estimate concentrations of copper in drinking water, volumes of drinking water consumed by children, and children's daily intake of copper. Concentrations of copper in unflushed drinking water were analyzed for 1,178 children living in Uppsala and Malmo, Sweden, and concentrations and amounts of copper consumed from drinking water were estimated for 430 of these children, 9-21 months of age. The study children were from Swedish families, were not enrolled in publicly provided day care, and were not breast-fed more than three times a day. In the initial population, the 10th percentile for copper concentration in unflushed drinking water was 0.17 mg/L, the median was 0.72 mg/L, and the 90th percentile was 2.11 mg/L. In the subpopulation of 430 children, the 10th percentile for daily intake of copper from drinking water was 0.03 mg/L, the median was 0.32 mg/L, and the 90th percentile was 1.07 mg/L. The median daily intake of copper from drinking water was higher in Uppsala, at 0.46 mg, than in Malmo, at 0.26 mg. For groups of children whose families took part in a later prospective diary study, the copper concentration in consumed water could, to some extent, be predicted from the concentration of copper in unflushed drinking water. The lowest concentrations of copper in drinking water were found in households with old water-pipe systems and in those living in detached houses. A large proportion of the young children satisfied their daily requirement of copper solely from drinking water. About 10% of the children had a copper intake above the level recommended by the World Health Organization. (+info)
Feeding and watering behavior of healthy and morbid steers in a commercial feedlot.
(22/1487)
Our objective was to determine whether there were differences in feeding and watering behavior of newly received healthy and morbid feedlot steers. Two separate 32-d feeding trials were conducted in Wellton, Arizona, in July and November 1996. Radio frequency technology was used to record individual animal behaviors from 108 (average weight 139 kg) and 143 (average weight 160 kg) steers in each respective trial. Steers that were subsequently identified as morbid were present at the feed bunk in greater percentages than reported in previous studies. In Trial 1, healthy steers spent more (P < .001) time at the feed bunk and had more (P < .009) feeding bouts than morbid steers. In Trial 2, healthy steers did not spend more time at the feed bunk, but they had more (P < .02) daily feeding bouts than morbid steers. There were no differences in daily time spent at the water trough by healthy or morbid steers in either trial. The greatest proportion of feeding and watering behavior occurred during the daylight hours in response to feed delivery. The pattern of time spent at the feed bunk throughout the 32-d feeding period was similar for healthy and subsequently morbid steers, but healthy steers had more feeding bouts per day. (+info)
Effects of delta 9-tetrahydrocannabinol and diazepam on feeding behavior in mice.
(23/1487)
The present study examined effects of diazepam (DZP) alone or in combination with delta 9-tetrahydrocannabinol (THC) on feeding behavior as well as body weight in male ddY strain mice at 5 weeks of age. Because we saw no hyperphagic effect of DZP with or without THC in mice, we explored the hyperphagia elicitable by DZP. THC [2 (THC2) or 4 (THC4) mg/kg/day s.c.] was given daily for 7 days. For the last day the mice were starved and injected i.p. with DZP (2 mg/kg) 10 min prior to a food or maze test. Controls received vehicle injections. Feeding behavior was measured after giving food for 2 hr. THC4 significantly reduced body weight gain. DZP, with or without THC, induced hyperphagia. THC4 alone also induced hyperphagia that was not significantly affected by DZP. Time taken to find food was extended by DZP and further with THC. Both DZP and THC can therefore interact on food ingestion but synergize on food seeking in mice through different mechanisms. (+info)
Motor activity changes in scrapie-affected mice.
(24/1487)
Measurements of spontaneous motor activity using Animex equipment have been made throughout the incubation period in mice developing scrapie. A progressive fall in activity has been noted from an early stage in the disease process well before clinical signs of scrapie were evident. The initial fall was followed by an upsurge in activity at about the time when clinical signs of disease develop. (+info)