Hypotensive action of parathyroid hormone preparations on rats and dogs.

Abstract

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 ...

Mechanism of acute hypercalcemic hypertension in the conscious rat.

“…In the present study a potential role of vasodepressor hormones such as the prostaglandins 31 and parathyroid hormone 32 in attenuating the hypertensive response to acute hypercalcemia was also investigated. In rats pretreated with the cyclooxygenase inhibitor indomethacin the hypertensive response to acute hypercalcemia was not altered.…”

“…Alternatively, vasodilative hormones such as prostaglandins 31 and parathyroid hormone 32 could attenuate the pressor response to acute hypercalcemia. In this respect, recent studies have shown that calcium enhances prostaglandin synthesis.…”

Hypertensive effect of calcilytic NPS 2143 administration in rats

“…The known effect of the single doses of 1-34 PTH (Pang et al 1980, Saglikes et al 1985, Baksi 1988 or 1-84 PTH (Saglikes et al 1985) is the activity that transiently decreases blood pressure in intact (Pang et al 1980, Saglikes et al 1985 or thyroparathyroidectomized (Baksi 1988) animals. In these experiments, the decrease in blood pressure was observed immediately, within about 1 min, after PTH injection.…”

High Blood Pressure, Bone-Mineral Loss and Insulin Resistance in Women

“…However, other studies have not demonstrated such elevations in hypertensive subjects (7). Acute administration of PTH results in decreased blood pressure (27) and relaxation of vascular tissue (28), suggesting that PTH is a direct vasodilator. By contrast, long-term attenuation of PTH by parathyroidectomy prevents the normal age-related increases in blood pressure in hypertensive and normotensive animals (29).…”