Central alpha 2-adrenoceptor responsiveness in borderline hypertensive rats.

Increased dietary NaCl intake increases the responsiveness of central nervous system alpha 2-adrenoceptors which regulate the neural control of renal function in spontaneously hypertensive rats (SHR) but not Wistar-Kyoto (WKY) normotensive rats. The borderline hypertensive rat (BHR) is the first filial offspring of the SHR and the WKY. With increased dietary NaCl intake, the BHR develops hypertension and expresses other characteristics of the hypertensive SHR parent. This investigation sought to determine whether increased dietary NaCl intake in the BHR enhances the responsiveness of central nervous system alpha 2-adrenoceptors. Six weeks of increased dietary NaCl intake (8% versus 1% NaCl) in BHR augmented the depressor, bradycardic, renal sympatho-inhibitory and diuretic responses to intracerebroventricular administration of graded doses (5, 25 and 125 micrograms) of the alpha 2-adrenoceptor agonist, guanabenz. The results suggest that the potential for an increased responsiveness of central nervous system alpha 2-adrenoceptors is genetically transmitted to the BHR by the SHR and may be exposed in the BHR by increased dietary NaCl intake.     

Direct evidence for the involvement of carbohydrate sequences in human sperm-zona pellucida binding

Several lines of evidence indicate that mammalian fertilization is initiated via a binding process that is dependent upon the recognition of oligosaccharide sequences associated with zona pellucida (ZP) glycoproteins. Here, specific chemical and enzymatic methods were employed to modify human ZP and to test their effects on sperm binding in the hemizona assay system (HZA). Periodate oxidation of human ZP under very mild conditions (10 min, 0 degrees C, 1 mM sodium m- periodate) that attacks only terminal sialic acid resulted in a 30% loss of human sperm binding in the HZA [hemizona index (HZI) = 70.2 +/- 10.9, n = 22; P < 0.05]. Periodate oxidation under mild conditions (1 h, 23 degrees C, 10 mM sodium m-periodate) caused a 40% decrease in binding (HZI = 60.8 +/- 10.3; n = 24; P< 0.01). Treatment of human ZP with neuraminidase caused a substantial increase in sperm binding to human ZP (HZI = 297 +/- 45, n = 22; P < 0.01). These findings indicate that there are sialic acid dependent binding sites coexisting with binding sites that are obscured by sialic acid. To determine the periodate sensitivity of these obscured sites, hemizona were first digested with neuraminidase and subsequently subjected to mild periodate oxidation. The combined enzymatic and chemical treatments caused a 79% decrease in sperm binding compared to control hemizona (HZI = 20.7 +/- 4.4, n = 16; P < 0.001). Human sperm-ZP interaction was also increased by digestion of human ZP with endo-beta-galactosidase (HZI = 710 +/- 232, n = 14; P < 0.01), indicating that potential binding sites for spermatozoa are also obscured by lactosaminoglycan sequences. These studies support a definitive role for the involvement of ZP-associated glycans in the binding of human spermatozoa to oocytes.      

Renal neuroadrenergic transmission.

To study the role of the renal sympathetic nerves in the regulation of sodium excretion, we examined the renal functional response to left renal nerve stimulation before (group I) and after (group II) left renal adrenergic blockade with guanethidine. In group I dogs, absolute sodium excretion from the left kidney fell markedly after left renal nerve stimulation; the decreases in glomerular filtration rate and renal blood flow were of a similar magnitude. Using the radiolabeled microsphere technique, distribution of renal blood flow to the outer cortex was diminished after left renal nerve stimulation. In group II dogs, guanethidine blocked all of these effects of left renal nerve stimulation. In group iii studies, a low level of left renal nerve stimulation was used which resulted in a decrease in sodium excretion in the absence of changes in glomerular filtration rate, renal blood flow, or intrarenal distribution of blood flow; this effect was blocked by renal adrenergic blockade with guanethidine in group iv studies. These data support a role for the renal sympathetic nerves to directly influence renal tubular sodium transport in the absence of alterations in renal hemodynamics.     

Effect of magnesium on sodium transport in toad urinary bladder.

Voltage-clamp techniques were employed to examine the effect of magnesium (Mg) on sodium transport in the isolated urinary bladder of the Dominican toad. Substitution of 1 mM Mg had no effect, but 3-mM Mg substitution resulted in a reversible increase in short-circuit current (27%) and potential difference (19%) and decrease in transepithelial resistance (14%); no greater effect was seen with 5- or 10-mM Mg substitution. The effect was produced by mucosal or mucosal and serosal Mg substitution; serosal Mg substitution was without effect. Analysis of electrical parameters disclosed that magnesium increased net sodium transport via an effect on the sodium pump.     

Combined antioxidant and COMT inhibitor treatment reverses renal abnormalities in diabetic rats

The development and progression of diabetic nephropathy is dependent on glucose homeostasis and many other contributing factors. In the present study, we examined the effect of nitecapone, an inhibitor of the dopamine-metabolizing enzyme catechol-O-methyl transferase (COMT) and a potent antioxidant, on functional and cellular determinants of renal function in rats with streptozotocin-induced diabetes. Administration of nitecapone to diabetic rats normalized urinary sodium excretion in a manner consistent with the dopamine-dependent inhibition of proximal tubule Na,K-ATPase activity. Hyperfiltration, focal glomerulosclerosis, and albuminuria were also reversed by nitecapone, but in a manner that is more readily attributed to the antioxidant potential of the agent. A pattern of elevated oxidative stress, measured as CuZn superoxide dismutase gene expression and thiobarbituric acid-reactive substance content, was noted in diabetic rats, and both parameters were normalized by nitecapone treatment. In diabetic rats, activation of glomerular protein kinase C (PKC) was confirmed by isoform-specific translocation and Ser23 phosphorylation of the PKC substrate Na,K-ATPase. PKC-dependent changes in Na,K-ATPase phosphorylation were associated with decreased glomerular Na,K-ATPase activity. Nitecapone-treated diabetic rats were protected from these intracellular modifications. The combined results suggest that the COMT-inhibitory and antioxidant properties of nitecapone provide a protective therapy against the development of diabetic nephropathy.     

Colonic motility diagnosis based on colonic pressure

Manometry of the alimentary tract is a valuable and widely used means to evaluate and diagnose the function of the alimentary tract. However, the measurement can be inconvenient due to the invasive method used, and the many factors affecting results. Research on colonic pressure data is even more insufficient. This paper deals with colonic pressure data via an improved method ensuring that pressure data of the whole colon is available. The data is analysed based on the learning vector quantization (LVQ) method. Testing results show that this method distinguishes the normal data and the abnormal data, consistently with the original diagnoses. This method can serve as an assistant diagnosis of colonic motility and contributes to further research on colonic motility based on pressure data.