Short-term study of the uptake of PrP(Sc) by the Peyer's patches in hamsters after oral exposure to scrapie.

The disease-associated prion protein (PrP(Sc)) has been detected in the ileal Peyer's patches of lambs as early as one week after oral exposure to scrapie. In hamsters, the earliest reported time of PrP(Sc) detection in the Peyer's patches after oral exposure to scrapie is 69 days post-infection. To evaluate the acute uptake of inoculum and to investigate whether the Peyer's patches constitute the primary site of entry for scrapie after oral exposure, hamsters were each exposed orally to 1 ml of a 10% brain homogenate from hamsters in the terminal stage of infection with the 263 K strain of the scrapie agent. PrP(Sc) was demonstrated in the Peyer's patches only a few days after exposure, i.e., much earlier than previously reported. This study supports the view that the Peyer's patches constitute at least one of the primary entry sites of PrP(Sc) after oral exposure to scrapie.

Effects of oophorectomy on functional properties of resistance arteries isolated from the cancellous bone of the rabbit femur.

Information is sparse concerning the effect of oophorectomy (OOX) on bone vascularization and blood flow of possible significance for altered remodeling. Whether OOX affects functional characteristics of isolated bone resistance arteries was investigated. Ring preparations (diameter approximately 250 microm) of small femoral bone arteries from oophorectomized and sham-operated rabbits were mounted on a myograph six weeks postoperatively. Cumulative concentration response curves were obtained for various agonists at a normalized lumen diameter. Oophorectomy did not significantly influence lumen diameter, maximal response to high potassium, or maximal response to high potassium and 10(-5) M noradrenaline. However, OOX significantly increased the maximal response to noradrenaline (OOX 2.14 +/- 0.36 N/m, Sham 1.25 +/- 0.14 N/m) and endothelin-1 (OOX 1.76 +/- 0.32, Sham 0.95 +/- 0.15) in metaphyseal arteries. Moreover, the corresponding maximal active pressure for the agonists was significantly increased. OOX did not influence endothelial function assessed by the effects of acetylcholine or substance P. The functional responses of diaphyseal arteries were unaffected by OOX. The study demonstrates regional differences in the effects of OOX on small arteries of importance for control of vascular resistance in bone which suggests a relation between altered vascular function after ovarian hormonal withdrawal and the changes in bone turnover associated with osteoporosis.

The effect of oophorectomy on mechanical properties of rabbit cerebral and coronary isolated small arteries.

OBJECTIVE: Our purpose was to study the effect of oophorectomy on the passive and active mechanical characteristics of rabbit small cerebral and small coronary arteries. STUDY DESIGN: Ring preparations of small cerebral and small coronary arteries from rabbits that had undergone oophorectomy and sham operation were mounted on myographs 6 weeks after operation. Experiments were performed as follows. (1) concentration-response relations for vasopressin (10(-11) to 10(-7) mol/L), U46619 (10(-10) to 10(-6) mol/L), 5-hydroxytryptamine (10(-7) to 10(-5) mol/L), and endothelin (10(-13) to 10(-7) mol/L); (2) relaxing effects of acetylcholine (10(-8) to 10(-4) mol/L); (3) length-tension relations after addition of high potassium (124 mmol/L), vasopressin (10(-7) mol/L), and a mixture composed of potassium (124 mmol/L), vasopressin (10(-7) mol/L), and prostaglandin F 2 alpha (10(-5) mol/L); (4) calculation of vessel morphologic features and determination of hydroxyproline as a measure of collagen content. RESULTS: Oophorectomy did not influence basal tone, relaxant effects of acetylcholine, vessel morphologic features, elastic characteristics, or hydroxyproline content of the vessels. However, in cerebral arteries at a normalized lumen diameter, oophorectomy induced a marked increase in the force development after stimulation with agonists but not after depolarization with high potassium. The reason for this was a leftward shift in the active length-tension curves (vasopressin activation). In coronary arteries none of these changes were seen after oophorectomy. CONCLUSION: These data demonstrate that withdrawal of ovarian hormones changes the position of the active length-tension curve for pharmacomechanical but not electromechanical coupling of small cerebral arteries without interference with the elastic characteristics of these vessels.

Angiotensin-converting enzyme activity and contractile effects of angiotensin I and II in human uteroplacental arteries.

OBJECTIVE: Our purpose was to study local angiotensin-converting enzyme activity and the mechanical effects of angiotensin I and II in human uteroplacental arteries. STUDY DESIGN: Angiotensin-converting enzyme activity was measured by a simple radioimmunoassay with tritiated benzoyl-glycyl-glycyl-glycine as substrate in isolated human intramyometrial arteries from nonpregnant (n = 8) and term pregnant women (n = 8) and placental (n = 8) stem villous arteries. Moreover, in these vessels the mechanical effects of angiotensin I and II were investigated in organ bath experiments. Endothelium-intact and endothelium-denuded arteries were used, and the integrity of the endothelium was examined by histologic studies. RESULTS: The activity of angiotensin-converting enzyme ranked the intramyometrial arteries from pregnant women >> intramyometrial arteries from nonpregnant women > fetal stem villous arteries. Angiotensin-converting enzyme activity was unaffected by removal of the endothelium. Angiotensin II 10(-5) mol/L produced contractile responses in the intramyometrial arteries without significant differences between arteries from nonpregnant and pregnant women. In fetal stem villous arteries the effects of angiotensin II 10(-5) mol/L were less pronounced. As for angiotensin II, the contractile responses to angiotensin I 10(-5) mol/L showed marked development of tachyphylaxis. In the endothelium-denuded preparations the contractile responses to angiotensin I 10(-5) mol/L were significantly enhanced in intramyometrial arteries from nonpregnant women but remained unchanged in intramyometrial arteries from pregnant women and in fetal stem villous arteries. In all preparations pretreatment with captopril or perindopril (10(-5) mol/L) markedly reduced angiotensin-converting enzyme activity, whereas no effects were observed on the contractile responses to angiotensin I. Saralasin 10(-5) mol/L completely abolished the contractile responses to angiotensin I and II. CONCLUSION: Local angiotensin-converting enzyme activity in human intramyometrial arteries seems to be markedly increased during pregnancy and shows marked differences between maternal and fetal uteroplacental arteries. High concentrations of angiotensin I may imply direct effects on the angiotensin II receptor independent of the local angiotensin-converting enzyme activity.