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Biomedical subjects

S G Wei

Publications and source records attributed to S G Wei.

9 recordsLinked to original sources

Neurohumoral regulation in ischemia-induced heart failure. Role of the forebrain.

Congestive heart failure (CHF) is characterized by neurohumoral excitation. Increased sympathetic drive and activation of the reninangiotensin-aldosterone system (RAAS), with vasoconstriction and volume retention, are hallmarks of the CHF syndrome. Treatment strategies have targeted the peripheral influences of these two systems, but have not addressed the central mechanisms that drive them. We monitored the development of CHF following coronary ligation in adult Sprague-Dawley rats. Left ventricular dysfunction characteristic of CHF was confirmed by echocardiography, and the CHF syndrome was validated by measurements of circulating hormones, sodium appetite, thirst, renal sodium and water retention, and renal sympathetic nerve activity (RSNA). In CHF rats, neuronal activity in the hypothalamic paraventricular nucleus (PVN), which mediates downstream effects of forebrain circumventricular organs, was increased and was inhibited by blocking components of the RAAS at the forebrain level. Forebrain (AV3V) lesions and intracarotid (forebrain directed) injections of agents (captopril, losartan, spironolactone) that block RAAS substantially attenuated the behavioral and physiological manifestations of CHF. Intravenous losartan and captopril, in doses that lower arterial pressure, increased RSNA. These findings demonstrate an important role for RAAS-activated forebrain mechanisms in CHF and suggest that the central neural mechanisms driving sympathetic nerve activity and volume retention may persist and promote the progression of CHF despite treatments directed toward the peripheral influences of RAAS.

Animals↗

Central mineralocorticoid receptor blockade improves volume regulation and reduces sympathetic drive in heart failure.

The mineralocorticoid (MC) receptor antagonist spironolactone (SL) improves morbidity and mortality in patients with congestive heart failure (CHF). We tested the hypothesis that the central nervous system actions of SL contribute to its beneficial effects. SL (100 ng/h for 28 days) or ethanol vehicle (VEH) was administered intracerebroventricularly or intraperitoneally to rats with CHF induced by coronary artery ligation (CL) and to SHAM-operated controls. The intracerebroventricular SL treatment prevented the increase in sodium appetite and the decreases in sodium and water excretion observed within a week of CL in VEH-treated CHF rats. Intraperitoneal SL also improved volume regulation in the CHF rats, but only after 3 wk of treatment. Four weeks of SL treatment, either intracerebroventricularly or intraperitoneally, ameliorated both the increase in sympathetic drive and the impaired baroreflex function observed in VEH-treated CHF rats. These findings suggest that activation of MC receptors in the central nervous system plays a critical role in the altered volume regulation and augmented sympathetic drive that characterize clinical heart failure.

Animals↗

Progression of heart failure after myocardial infarction in the rat.

This study examined the early neurohumoral events in the progression of congestive heart failure (CHF) after myocardial infarction (MI) in rats. Immediately after MI was induced by coronary artery ligation, rats had severely depressed left ventricular systolic function and increased left ventricular end-diastolic volume (LVEDV). Both left ventricular function and the neurohumoral indicators of CHF underwent dynamic changes over the next 6 wk. LVEDV increased continuously over the study interval, whereas left ventricular stroke volume increased but reached a plateau at 4 wk. Plasma renin activity (PRA), arginine vasopressin, and atrial natriuretic factor all increased, but with differing time courses. PRA declined to a lower steady-state level by 4 wk. Six to 8 wk after MI, CHF rats had enhanced renal sympathetic nerve activity and blunted baroreflex regulation. These findings demonstrate that the early course of heart failure is characterized not by a simple "switching on" of neurohumoral drive, but rather by dynamic fluctuations in neurohumoral regulation that are linked to the process of left ventricular remodeling.

Animals↗

[Effect of electrical stimulation of afferent renal nerve on arterial blood pressure, heart rate and vasopressin in rabbits].

The effect of electrical stimulation of afferent renal nerve (ARN) on cardiovascular response, the synthesis and release of vasopressin were studied in rabbits. During the course of the experiment, the pathway of ARN to central nerve system was also analyzed. The results showed that electrical stimulation of ARN elicited significantly decrease of mean arteral blood pressure and heart rate as well as inhibition of cervical sympathetic nerve activity. In the event of the above physiological changes, the AVP concentration in supraoptic nucleus (SON), paraventricular nucleus (PVN) and plasma was increased, but that in hypophysis was decreased. Injection of sodium nitropruside (SNP) or AVPa indicated that increase of AVP release was due directly to stimulation of ARN. Nodose ganglionectomy or transversal section of spinal cord at different levels suggested that the main afferent pathway of ARN to higher level of central nerve system entered into spinal cord at T5-L2.

Afferent Pathways↗

[Reversal of malignant phenotype of human hepatoma cells by antisense c-ets-2, c-myc and N-ras].

A recombinant retroviral vector was constructed which expressed antisense RNA of c-ets-2, c-myc and N-ras. The pseudotype virus was packaged and rescued by transfection in PA317 cells and used to infect human hepatoma cell line SMMC-7721. After selection with G418, resistant colonies were obtained. Stable integration of retrovirus in infectants was shown by Southern hybridization of genomic DNA and the presence of antisense RNA was detected by RNA dot blot hybridization. It was demonstrated that the antisense RNAs did inhibit the growth of human SMMC-7721 hepatoma cells. The ability to form colony in soft agar and tumorigenicity in nude mice of SMMC-7721 were significantly suppressed by the antisense RNAs. The result implicates the potential value in future cancer gene therapy.

Animals↗

Calpastatin gene in human testis.

Antibodies present in a serum obtained from an infertile woman interacted with a 17.5 kD glycoprotein (BS-17 component) extracted from human sperm by Western blot. Polyclonal antibodies were raised against the BS-17 component and used to identify positive staining clones from a human testis lambda gt11 expression library. The cDNA encoding the BS-17 component was isolated and its nucleotide sequence determined. The BS-17 cDNA contained 758 nucleotides with an open reading frame of 558 nucleotides encoding a polypeptide consisting of 186 amino acids. The BS-17 cDNA showed 99.7% homology in 758 nucleotides overlap with the 3' terminus of the gene coding calpastatin and 99.5% identity in 186 amino acid overlap with the carboxyl terminus of calpastatin. The BS-17 component of human sperm corresponds to the carboxyl terminus of calpastatin. This conclusion is supported by the finding that the polyclonal antibodies also interacted with a 84 kD protein corresponding to the M(r) of calpastatin.

Amino Acid Sequence↗

[Modulatory role of the cerebellar cortex during the classically conditioned nictitating membrane response in rabbit].

Classical conditioning of the rabbit nictitating membrane(NM) response was accomplished by standard delay procedure of paired tone (CS) and airpuff (US) stimuli. Upon reaching a criterion of 90% conditioned responses (CRs) in 3 consecutive blocks, an electrolytic lesion was made at the hemicerebellar VI cortical lobule on the training side. Results showed that the learned response of the dentate-interpositus (D-I) nuclei and the conditioned NM response were completely or almost completely eliminated without affecting the unconditioned response. However, cerebellar cortical lesion performed on animals being over 1 week overtrained produced no effect on CRs and the learned response of the D-I nuclei. Meanwhile, the spontaneous activity of the D-I nuclei during consolidation reduced in frequency as a result of the cortical lesion at the early stage of learning. Our findings indicate that the cerebellar cortex plays a modulatory role in the generation of the conditioned NM response and the development of the learned response of the D-I nuclei at an early stage of learning. With consolidation, the D-I nuclei become free of control from the cerebellar cortex and serve as the essential component of the memory trace for this model system.

Animals↗

Fertility studies with antisperm antibodies.

Serum obtained from an infertile subject possessed antibodies that interacted with a human sperm glycoprotein with an estimated M(r) of 17,550 and pI of 5.65 containing 17.7% neutral hexoses and designated as the BS-17 component. Polyclonal antibodies raised against the BS-17 antigen blocked the capacity of human sperm to fertilize zona-free hamster ova in vitro; however, the antibodies did not influence the binding of human sperm to zone-free ova or alter the motility of human sperm. The antibodies inhibited the capacity of mouse sperm to fertilize ova upon in vivo insemination. The BS-17 antigen was detected in human, rat, mouse, rabbit, and hamster sperm by an immunocytochemical method, using polyclonal anti-BS-17 antibodies. Intense staining occurred over the surface of the acrosomal region of all mammalian sperm. The results suggest that the production of anti-BS-17 antibodies contribute to infertility by preventing the capacitation of sperm and/or by blocking the ability of capacitated sperm to fertilize the egg.

Animals↗

Expression of the calpastatin gene segment during spermiogenesis in human testis: an in situ hybridization study.

Serum obtained from an infertile woman contained antibodies that agglutinate human sperm. The antibodies interacted with a sperm protein with an estimated M(r) of 17.5 kD. The cDNA coding the 17.5-kD protein was isolated from a human testis lambda gt11 expression library and identified as a segment of the calpastatin gene. Single-stranded 35S-labeled RNA probes were prepared from the calpastatin cDNA segment. Using the techniques of in situ hybridization, the calpastatin mRNA was located in spermatids of human testis. The results support a previous observation that the calpastatin segment is produced during spermiogenesis and suggest that transcription of the calpastatin gene occurred during the postmeiotic haploid stage of spermatogenesis.

Calcium-Binding Proteins↗