Bovine parathyroid extract and two commercial preparations containing the first 34 amino acids of synthetic bovine parathyroid hormone [bPTH41-34)] produced dose-related hypotension in anesthetized rats. Dogs were 10 times more sensitive to the two bPTH41-34) preparations than were rats.Propranolol, phentolamine, atropine, and promethazine did not affect the hypotensive action of bPTH-1-34) in rats and dogs. bPTH-1-34) decreased perfusion pressure in rat hindlimbs perfused in situ with Ringer's solution and was a vasodilator in dog kidneys perfused in vitro with Ringer's solution. Helical strips of rabbit aorta were also relaxed by bPTH41-34). We conclude that the direct vasodilatory action of bPTH preparations represents an intrinsic property of parathyroid hormone and that the hypotensive effect of this hormone is produced by part or all of the first NH2-terminal 34 amino acids.The antidiuretic action of exogenous parathyroid preparations in the South American lungfish (Lepidosiren paradoxa) was described in a previous report (1). Because renal function in lungfish is significantly affected by systemic blood pressure (2, 3), we suspected that the antidiuresis resulting from administration of parathyroid extracts might be related to a hypotensive action of this hormone. A vasodilatory action of parathyroid extract and the peptide containing the first 34 amino acids of synthetic bovine parathyroid hormone ] has been reported in dogs (4, 5). This hypotensive action of parathyroid hormone (PTH) has not been confirmed in any other vertebrate species. Furthermore, it was not clear whether the hormone is itself hypotensive or whether its action is mediated through other endogenous vasoactive substances.In a recent series of studies, we observed the vasodepressor actions of synthetic bPTH-(1-34) in the following vertebrates: the South American lungfish, the bullfrog, the water snake Natrix fasciata, and the domestic chicken (6). In the present studies we investigated the specific hypotensive actions of bPTH in the laboratory white rat and the mongrel dog. A dose-related vasodepressor response was demonstrated with two preparations of synthetic bPTH-(1-34). In both rats and dogs, the hypotensive action of bPTH-(1-34) was not inhibited by a-or 3-adrenergic, cholinergic, or histaminergic blocking agents. Furthermore, vasodilation could be demonstrated by using dog kidneys in vitro and rat hindlimbs perfused in situ with mammalian Ringer's solutions. Helical strips of rabbit aorta were also relaxed by bPTH-(1-34). On the basis of these results we propose that mammalian PTH has an intrinsic direct vasodilatory action on the vascular system. The exact mechanism of this action remains to be demonstrated. MATERIALS AND METHODSThree types of experiments were performed. Dogs and rats were used to determine the depressor effect of bPTH preparations in vivo. To test the vasodilatory effects of the synthetic bPTH-(1-34) in vitro, dog kidneys and rabbit aortic strips were perfused. In addition, rat hindlimbs were perfused ...

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The present study was conducted to show that the hypercalcemic and the vascular relaxing activities of PTH are two separable properties. During the hypotensive action of the synthetic fragment bovine (b) PTH-(1-34), plasma calcium levels were not significantly changed. Mild oxidation with hydrogen peroxide abolished the hypotensive and hypercalcemic actions of bPTH-(1-84). However, the same treatment on bPTH-(1-34) abolished only the hypotensive and not the hypercalcemic action. Analysis of the amino acid composition revealed only the oxidation of the methionines to methionine sulfoxides. The other amino acids remained unchanged. In addition, the analog with methionines replaced by norleucine, [Nle8,Nle18,Tyr34]bPTH-(1-34), was active in all the vascular assays, and these activities were unaffected by hydrogen peroxide treatment of the molecule. Perhaps the methionine sulfoxides in the hydrogen peroxide-treated bPTH-(1-34) affected the changes of the molecule in such a manner that the part of the molecule for the vascular action but not that for the hypercalcemic action was no longer accessible to the receptors of the target organs. The hypotensive pentapeptide, bPTH-(24-28), was not active in the hypercalcemic assay. All these data are consistent with our hypothesis that the vascular relaxing and the hypercalcemic actions of PTH are two separate properties of the molecule.

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The hemodynamic effects of long-term administration of octreotide in portal hypertension has not been established. In addition, whether long-term octreotide treatment prevents the development of portosystemic shunts has not yet been evaluated. Hence, the current study was undertaken to evaluate the effects of long-term administration of octreotide in rats with portal vein stenosis. Immediately after portal vein stenosis or sham operation, rats were given either a long-term octreotide administration of 100 micrograms/kg or a placebo every 12 hours by subcutaneous injection for 14 consecutive days. Systemic hemodynamics and regional blood flows, degree of mesenteric-systemic shunts, and plasma glucagon concentrations were measured after the final dose of octreotide or placebo. A fifth group of portal vein-stenosed rats received hemodynamic and plasma glucagon measurements after 1-day octreotide treatment given at 14 days after surgery. Long-term octreotide treatment modified the hyperdynamic circulation without affecting the degree of mesenteric-systemic shunts, and 1-day octreotide treatment decreased portal tributary blood flow without affecting the portal pressure, systemic hemodynamics, and degree of mesenteric-systemic shunts. Plasma glucagon levels were decreased in portal vein-stenosed rats receiving either long-term or 1-day octreodtide compared with rats receiving placebo. In contrast, chronic octreotide treatment did not affect any of the hemodynamic values or plasma glucagon levels in sham-operated rats. In conclusion, long-term administration of octreotide modified in part the development of portal hypertension and hyperdynamic circulation in portal vein-stenosed rats without affecting the degree of mesenteric-systemic shunts.

1 Vascular hyporesponsiveness in portal hypertension has been demonstrated to various vasoconstrictors including noradrenaline (NA). The present study aimed to determine whether the attenuated vascular responsiveness to NA is due to a change in the affinity or the number of ol-adrenoceptors.

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