The cryoprotective effect of sucrose has been investigated using 3 different vascular smooth muscle preparations, namely canine saphenous veins and arteries and porcine circumflex coronary arteries following storage in liquid nitrogen (at -196 degrees C). Contractile responses to noradrenaline, 5-HT, prostaglandin F2 alpha and KCl and relaxant responses to substance P and 5-HT were determined on fresh tissues and after cryostorage in fetal calf serum (FCS) containing either 1.8 M dimethyl sulfoxide (DMSO), or 0.1 M sucrose or both agents combined. The data demonstrate that the addition of sucrose to the DMSO-containing cryomedium promotes the preservation of both contractile and relaxant activity of cryostored blood vessels, though sucrose alone did not confer any noticeable protection.
1 Human intrapulmonary arteries have been investigated in vitro in fresh tissue or after storage at -190'C in foetal calf serum containing 1.8 M dimethyl sulphoxide. 2 After cryopreservation of the arteries, maximal contractile force was reduced to 76%. This was assessed by the responses (in g) to 10 nm of the thromboxane analogue, U 46619. 3 Constricting agonists such as noradrenaline, 5-hydroxytryptamine, histamine and U 46619 stimulated fresh and frozen/thawed arteries producing pD2 values similar to the respective values determined on fresh tissues. 4 Endothelium-independent relaxant responses of U 46619-precontracted arteries to prostacyclin (PGI2), aminophylline and papaverine were generally unchanged after storage. The same was true for relaxant response to the potassium channel activator P-1075 whereas the pD2 values for SDZ PCO 400, RP 49356 and cromakalim were somewhat diminished. 5 Nevertheless, a significant correlation was obtained when the apparent pD2 values for all agonists on fresh and frozen/thawed tissues were compared (P < 0.001). 6 The evidence suggests that after cryopreservation of human intrapulmonary arteries at -190°C, mechanisms of both contraction and relaxation are well-maintained.
Muller-Schweinitzer, E., P. Ellis, and R. Ziegler: Venoconstrictor responses to ergosine and ergosinine: Evidence for the isomerization of ergosinine. Drug Dev. Res. 25~49-I 59, 1992.Ergosine and its D-isolysergic acid derivative ergosinine were investigated on canine saphenous veins both in vivo and in vitro. Following local i.v. infusion in vivo, about 5 times higher doses of ergosinine were necessary to produce the same venoconstrictor response as induced by ergosine. When administered orally, however, both ergot alkaloids were equi-effective. In vitro methiothepin, a 5-HT receptor blocker with high affinity for 5-HT, receptors, antagonized venoconstrictor responses to 5-HT and ergosine within the same concentration range, being significantly less potent when tested against norepinephrine. The reverse was true for the a,-selective adrenoceptor blocker yohimbine, which was significantly more potent against norepinephrine and ergosine than against 5-HT, suggesting that ergosine has affinity to both 5-HT, -like receptors and a,-adrenoceptors. Concentration-response curves to norepinephrine were shifted to the right in a parallel fashion when ergosine or ergosinine were present in the organ baths, suggesting competitive antagonism. The blocking potency of ergosinine increased with increasing incubation times in Krebs-Henseleit solution becoming similar to that of ergosine when an incubation time of 2 hr was applied. It is suggested that the pharmacological activity of ergosinine is the consequence of an isomerization into its natural stereoisomer ergosine, which may occur both in vivo and in vitro.
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