PubMed Health⌕ Search

Biomedical subjects

R A Markle

Publications and source records attributed to R A Markle.

10 recordsLinked to original sources
PubMed1996

Streptozotocin-induced diabetes produces a decrease in pituitary substance P content and preprotachykinin mRNA.

Complications arising from diabetes mellitus include hormonal dysfunctions such as impairment in the regulation of gonadatroph and corticotroph secretion. Preprotachykinin (PPT) mRNA encoding the peptide substance P (SP), has been localized in the anterior pituitary. The goal of this study was to determine if streptozotocin (STZ)-induced diabetes affects the SP content or PPT mRNA level in the pituitary of male rats. We injected STZ (55 mg/kg) to 6-week-old rats which developed hyperglycemia (blood glucose > 400 mg/dl) by 6 weeks post-injection. SP-like immunoreactivity in the pituitary dropped 54%. In situ hybridization was performed using a PPT-specific oligonucleotide with signal intensity differences semi-quantified using an image analysis system. Normal pituitary had a regional distribution of PPT mRNA, with no detectable signal in the posterior or intermediate lobes, while the anterior lobe displayed a distinctive pattern of labeled cells arranged in clusters. In diabetic rats there was a 23% decrease in the PPT-mRNA hybridization signal compared to controls (P < 0.05). The changes observed in PPT gene expression and SP content may be additional factors participating in the hormonal complications seen in diabetes mellitus.

Animals↗
PubMed1996

Effects of streptozotocin-induced diabetes and insulin treatment on substance P of the rat arterial wall.

Substance P (SP) is present in perivascular nerves throughout the mammalian vasculature. Reports of diminished SP levels in nerve and gastrointestinal tissues of diabetic rats led us to examine SP-like immunoreactivity (SP-LI) in large arteries by RIA. Six weeks after inducing diabetes with streptozotocin (STZ), SP-LI was measured in the thoracic aorta, abdominal aorta, and the proximal superior mesenteric artery. In diabetics we measured a doubling (P<0.01) of SP-LI in all three artery wall preparations. This finding was verified in a second experiment which included a subset of diabetics treated daily with insulin for the sixth week of the holding period. Again, we measured a two-fold or greater increase of SP-LI (P<0.01-0.05) in arteries from the diabetics and found that insulin treatment significantly reduced SP-LI (P<0.05). In contrast to reports of diminished SP content in other tissues of diabetic rats, our findings demonstrate that the artery wall experiences at least a two-fold increase of SP-LI in the diabetic state. Furthermore, this elevation of SP-LI is reduced by insulin. We speculate that these changes of arterial wall SP-LI may contribute to altered regulation of the vascular system in the diabetic state.

Animals↗
PubMed1990

Substance P increases rat aortic albumin permeability.

We tested the hypothesis that exogenous substance P (SP) could enhance rat aortic permeability to plasma albumin. Fluorescein-labeled bovine serum albumin was used as the tracer. In vivo normalized albumin mass transfer rates (x10(-8) cm/sec) were 9.16 +/- 1.73, 14.20 +/- 2.76 (P less than 0.05) and 20.31 +/- 3.31 (P less than 0.001) for groups infused i.v. with 0.01 N acetic acid vehicle, 7.4 pmol and 0.74 pmol SP/kg/min for 5 min, respectively. No significant differences from the control group were found in rats receiving 150 pmol, 74 pmol nor 74 fmol SP/kg/min for 5 min. The results indicate that aortic permeability dynamics for plasma albumin can be enhanced by pmol levels of the tachykinin SP.

Animals↗
PubMed1989

Intrinsic focal variations of rabbit aortic hydrolase activities.

Normal arterial foci which take up Evans blue dye (EBD) in vivo are believed to represent atherosclerosis-prone, hemodynamically stressed foci compared to areas which exclude dye. We have used the rabbit EBD model to examine focal aortic hydrolases of blue areas versus white areas, and we report herein significant focal variations of hydrolase activities. Enzymes measured included neutral alpha-glucosidase, N-acetyl-beta-glucosaminidase, alpha-mannosidase, acid alpha-glucosidase, beta-galactosidase, beta-glucuronidase, cathepsin C, and acid cholesteryl esterase (ACE); specific activities were expressed on the basis of tissue DNA. In correlative areas of EBD uptake in normal rabbit aortic arch, ACE activity averaged 17% higher and cathepsin C activity averaged 37% lower than activities of areas free of EBD in the descending thoracic aorta (P less than 0.02). None of the glycosidases studied differed significantly between blue and white aortic areas. These findings indicate that discrete, intrinsic differences of hydrolytic enzyme activities exist in the normal rabbit aorta in areas delineated by in vivo EBD uptake, areas recognized as lesion-prone vs lesion-resistant.

Animals↗
PubMed1986

Renal histamine increases in the streptozotocin-diabetic rat.

Renal histamine concentration, total histamine and protein contents were measured in rats made diabetic via iv streptozotocin injection and held for 13 weeks following diagnosis of diabetes. Insulin (7 U/day) or alpha-hydrazinohistidine (alpha-HH, 25 mg/kg/day) or both drugs were administered to diabetic subgroups the last 2 weeks of the holding period. Untreated diabetics developed significant increases of renal histamine concentration and total histamine content, up 45 and 46%, respectively. Drug interventions reduced the diabetic increases of histamine concentration and content (in order) as follows: diabetic-insulin, down 7 and 8%; diabetic-alpha-HH down 25 and 26%; diabetic-insulin + alpha-HH, down 35 and 36%. Renal tissue protein content was unchanged and qualitative proteinuria was present in all diabetic subgroups. The data indicate that in experimental diabetes there is an increase of the renal inducible histamine pool which is partially reduced by insulin and/or alpha-HH treatments. In view of the long-recognized actions of histamine upon microvascular permeability, elevated renal histamine may be one pathophysiological mediator of the diabetic functional renal microangiopathy manifest as proteinuria.

Animals↗
PubMed1986

Hydrolase activities increase in the rat aorta with growth and aging but not in liver and kidney.

We examined specific activities (based on DNA) of six glycosidases and cathepsin C in aorta, kidney, and liver from male rats of 2, 6, 10, and 14 months of age. The premise was that assessing cellular catabolism of arterial and nonvascular tissues over age might more fully clarify the impact of age (and growth) alone upon vascular wall metabolism. All aortic glycosidases increased significantly (P less than 0.05) over the holding period as follows: neutral alpha-glucosidase, up 93%; beta-galactosidase, up 102%; N-acetyl-beta-glucosaminidase, up 119%; alpha-mannosidase, up 77%; beta-glucuronidase, up 65%; acid alpha-glucosidase, up 95%. Cathepsin C specific activity was unchanged as was aortic DNA content; total protein content increased 136%. In the kidney, all glycosidase specific activities declined over age with decreases ranging 39-55%; cathepsin C was unchanged. In the liver, neutral alpha-glucosidase increased 12%, acid alpha-glucosidase was unchanged, and the four remaining glycosidases decreased an average of 5-35% by 14 months of age. Liver cathepsin C decreased 44% over this period. Thus, enhancement of hydrolase baseline activities prevails during growth and aging in rat aortic tissue whereas hydrolases of kidney and liver tissues generally decline.

Acetylglucosaminidase↗
PubMed1981

Influence of locally altered in vivo shear stress on aortic histamine-forming capacity and aortic albumin uptake.

Effects of locally elevated shear stresses on thoracic histamine formation and transmural albumin uptake have been examined under in vivo conditions in anesthetized male, mongrel dogs. Results indicate that if endothelium remains intact, significant linear relationships exist between the shear intensity and aortic histamine-forming capacity and aortic content of fluorescein-labeled bovine serum albumin following 20 h of circulation time. These data suggest that in vivo the aortic (and endothelial) histidine decarboxylase system is sensitive to local alterations in applied shear stress, and that de novo aortic histamine synthesis in involved in mediating shear-induced increases in aortic transmural permeability.

Albumins↗
PubMed1978

Reversal of renovascular hypertension by antibodies specific for angiotensin-converting enzyme.

Goat antibodies developed against pure rabbit pulmonary angiotensin-converting enzyme (peptidyl dipeptidase, EC 3.4.15.1) were administered intravenously to rats with two-kidney Goldblatt hypertension and to normotensive animals. In the hypertensive model these antibodies were associated with a sustained, immune-dependent decrease of blood pressure to normal values. A smaller, but also immune-specific, reduction of blood pressure was observed in the normotensive group. The data suggest that heterologous antibody directed against angiotensin-converting enzyme may provide a biologically specific probe for examining the contribution of the renin-angiotensin system to normal and pathologic circulatory states.

Animals↗