Mechanism of systemic vasodilation during normovolemic hemodilution.

In the nonfailing heart, normovolemic hemodilution increases cardiac output and decreases total peripheral resistance (TPR). Putative mechanisms mediating the decrease in TPR include reflex vasodilation and changes in the local regulation of blood flow. Our objectives were to determine whether ablation of reflex neural mechanisms or the inhibition of nitric oxide (NO) synthase, the enzyme responsible for the synthesis of the endothelium-derived relaxing factor (EDRF-NO), modulates the systemic vasodilator response to normovolemic hemodilution. Three groups of male Sprague-Dawley rats were subjected to acute normovolemic hemodilution, which was achieved by exchanging a volume of blood equivalent to 3.8% of body weight with hydroxyethyl starch. Hemodilution increased cardiac output and decreased TPR. Subsequent administration of the NO synthase inhibitor, L-nitroarginine (LNA), returned both cardiac output and TPR to control values. Pretreatment with LNA prior to hemodilution increased TPR, an effect that was partially reversed by the NO donor, sodium nitroprusside. In this setting, hemodilution failed to decrease TPR. After spinal cord destruction by "pithing," hemodilution decreased TPR to the same extent as that observed in intact rats. This hemodilution-induced decrease in TPR was abolished by the subsequent administration of LNA. These results indicate that neural reflexes do not modulate the systemic vascular response to hemodilution. Moreover, the systemic vasodilator response to hemodilution is abolished after inhibition of endogenous NO synthesis.

Fentanyl stimulates atrial natriuretic peptide secretion.

The effects of fentanyl on ultrastructure, protein biosynthesis, and atrial natriuretic peptide (ANP) secretion were studied in neonatal rat cardiomyocytes (CM). Ventricles from 2-day-old American Wistar rats were digested with 1% collagenase in perfusion buffer. Eight hundred thousand to 1.0 million cells/ml were incubated in tissue culture media, to which fentanyl citrate (Sublimaze) was added in a dose of 10-50 ng/ml. Fentanyl increased the spontaneous CM beating rate, which became rather fibrillary in nature. Protein biosynthesis also increased in a time-related manner. Simultaneous incubation with naloxone (10(-6) M) did not alter the beating rate or protein synthesis. Ultrastructurally, several criteria of myocyte growth were observed: an increase in myofilaments and the appearance of newly formed organized sarcomeres, which were preceded by an increase in the ribosomes and cisternae of rough endoplasmic reticulum, and the appearance of large, adult-type mitochondria with increased matrix granules and long parallel cristae. The latter replaced the elongated thin fetal mitochondria. This was associated with a network of developing sarcoplasmic reticulum and T-tubular system as well as the formation of intercalated discs between the CM. Furthermore, exposure to fentanyl increased ANP immunoreactivity in the culture media while simultaneous incubation with naloxone blocked the effect of fentanyl on ANP secretion. On the other hand, naloxone alone did not alter ANP secretion. Therefore, it could be concluded that fentanyl stimulated protein biosynthesis and ANP secretion as evidenced both biochemically and ultrastructurally. Although the molecular mechanism of ANP secretion by fentanyl is still unclear, yet an opioid receptor mediation could be possible as ANP secretion was blocked by an opioid receptor antagonist (naloxone).

The localization of cholecystokinin immunoreactivity in the rat ovary and uterine tube.

The presence of cholecystokinin (CCK) immunoreactive nerve fibres in the rat ovary and uterine tubes was detected using the peroxidase antiperoxidase (PAP) technique. The antibody used was anti CCK 4562 which reacts with CCK-4, CCK-8, CCK-12 and CCK-33 (Larsson and Rehfeld, 1977). CCK-immunoreactive nerve fibres were found between the interstitial cells of the ovary, along blood vessels, and close to smooth muscle fibres in the ovary and tubal wall. A possible role of CCK-nerves in modulation of the sensitivity of the ovarian components to other humoral and nervous stimuli is discussed. The possible control of CCK over smooth muscle fibres in the ovary and the uterine tube and its role in ovulation is a matter of further studies.

Gold in the ovary of rats exposed to sodium aurothiomalate.

The ultrastructural localization of gold in the ovary of rats injected intraperitoneally with sodium aurothiomalate has been demonstrated using a histochemical technique that visualizes minute traces of gold. Gold was visualized in the oocyte within the cortical granules and in lysosomes of theca interna cells and interstitial cells.

The presence of smooth muscle cells in the rat ovary.

Using a histochemical procedure for the demonstration of glycogen phosphorylase, smooth muscle cells have been demonstrated in the rat ovary around follicles, corpora lutea, atretic follicles and between groups of interstitial cells.