pituitrin and talipexole

In order to analyse the effects of arginine-vasopressin on the vascular contraction to sympathetic nerve stimulation during cooling, the isometric response of isolated, 2-mm segments of the rabbit central ear (cutaneous) artery to electrical field stimulation (1-8 Hz) was recorded at 37 and 30 degrees C. Electrical stimulation (37 degrees C) produced frequency-dependent arterial contraction, which was reduced at 30 degrees C and potentiated by vasopressin (10 pM, 100 pM and 1 nM). This potentiation was greater at 30 than at 37 degrees C and was abolished at both temperatures by the antagonist of vasopressin V1 receptors d(CH2)5 Tyr(Me)AVP (100 nM). Desmopressin (1 microM) did not affect the response to electrical stimulation. At 37 degrees C, the vasopressin-induced potentiation was abolished by the purinoceptor antagonist PPADS (30 microM), increased by phentolamine (1 microM) or prazosin (1 microM) and not modified by yohimbine (1 microM), whilst at 30 degrees C, the potentiation was reduced by phentolamine, yohimbine or PPADS, and was not modified by prazosin. The Ca2+-channel blockers, verapamil (10 microM) and NiCl2 (1 mM), abolished the potentiating effects of vasopressin at 37 degrees C whilst verapamil reduced and NiCl2 abolished this potentiation at 30 degrees C. The inhibitor of nitric oxide synthesis, L-NOARG (100 microM), or endothelium removal did not modify the potentiation by vasopressin at 37 and 30 degrees C. Vasopressin also increased the arterial contraction to the alpha2-adrenoceptor agonist BHT-920 (10 microM) and to ATP (2 mM) at 30 and 37 degrees C, but it did not modify the contraction to noradrenaline (1 microM) at either temperature. These results suggest that in cutaneous (ear) arteries, vasopressin potentiaties sympathetic vasoconstriction to a greater extent at 30 than at 37 degrees C by activating vasopressin V1 receptors and Ca2+ channels at both temperatures. At 37 degrees C, the potentiation appears related to activation of the purinoceptor component and, at 30 degrees C, to activation of both purinoceptor and alpha2-adrenoceptor components of the sympathetic response.

Topics: Adenosine Triphosphate; Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Animals; Arteries; Azepines; Calcium Channel Blockers; Calcium Channels; Cold Temperature; Ear; Electric Stimulation; In Vitro Techniques; Muscle Contraction; Muscle, Smooth, Vascular; Norepinephrine; Phentolamine; Prazosin; Purinergic P2 Receptor Antagonists; Pyridoxal Phosphate; Rabbits; Receptors, Adrenergic; Sympathetic Nervous System; Vasoconstriction; Vasoconstrictor Agents; Vasopressins; Verapamil; Yohimbine

The effects of vasoactive substances on mean circulatory filling pressure (MCFP), an index of total body venous tone, were determined in conscious rats. Cumulative doses of saline (0.9% w/v NaCl solution), methoxamine (alpha 1-adrenoceptor agonist), B-HT920 (alpha 2-adrenoceptor agonist) noradrenaline and vasopressin, and individual doses of angiotensin II (AII), were infused into the rats. Mean arterial pressure (MAP), MCFP and heart rate (HR) were determined before and during the plateau responses to infusions of the vasoactive substances. The infusions of all the agonists caused a dose-dependent increase in MAP and a decrease in HR. The infusion of saline affected neither MAP nor HR. The infusions of saline and methoxamine did not affect MCFP while the infusions of B-HT 920, noradrenaline and AII increased MCFP. MCFP was slightly increased during the infusion of high doses of vasopressin. It was concluded that receptors for the alpha 2-adrenoceptor agonist and AII are involved in the control of venous tone. Receptors for the alpha 1-adrenoceptor agonist and vasopressin are not important for the control of venous tone.

Topics: Adrenergic alpha-Agonists; Angiotensin II; Animals; Azepines; Blood Pressure; Dose-Response Relationship, Drug; Heart Rate; Methoxamine; Norepinephrine; Rats; Rats, Inbred Strains; Vasopressins

The antihypertensive and hypotensive effects and the interaction with postjunctional alpha 1- and alpha 2-adrenoceptors of tibalosine were studied in various animal preparations. Tibalosine (CP 804 S, 1-10 mg/kg) elicited dose-dependent reductions in blood pressure upon i.v., oral or i.p. administration in conscious SEHR, in pentobarbitone-anaesthetized, normotensive rats, in chloralose-anaesthetized cats and in vasopressin-supported pithed normotensive rats. These reductions were not influenced by naloxone. Infusion via the vertebral artery of chloralose-anaesthetized cats (1 mg/kg) elicited a modest, centrally mediated reduction of blood pressure, which could be antagonized by yohimbine or naloxone, but not by prazosin. Intracerebroventricular application of tibalosine (3-300 micrograms/kg) to conscious SHR elicited pressor responses. In pithed normotensive rats, tibalosine inhibited the pressor responses to i.v. cirazoline (pA2 = 5.47 +/- 0.17), but not to those by i.v. B-HT 920 Tibalosine selectively displaced [3H]-prazosin from its specific binding site in rat isolated brain membranes. The present study identifies tibalosine as a highly selective alpha 1-adrenoceptor antagonist, 700-1000 times less potent than prazosin. The antihypertensive effect of tibalosine is most likely to be attributed to blockade of alpha 1-adrenoceptors in the peripheral circulation.

Topics: Adrenergic alpha-Antagonists; Animals; Antihypertensive Agents; Azepines; Brain; Cats; Clonidine; Female; Heart Rate; Injections, Intraventricular; Male; Membranes; Prazosin; Propanolamines; Rats; Rats, Inbred Strains; Vasopressins

The influence of tetrandrine on arterial pressure and heart rate of pentobarbitone-anaesthetized and conscious normotensive and hypertensive rats (SH rats, renal hypertensive rats, DOCA-salt hypertensive rats) was investigated. Tetrandrine administered intravenously (i.v.) to these animals caused an acute, long-lasting and dose-dependent decrease in mean arterial pressure. Heart rate was not significantly altered. In pithed rats, tetrandrine injected intraarterially 15 min previously impaired the increase in diastolic pressure induced by i.v. B-HT 920, a highly selective alpha 2-adrenoceptor-stimulating agent, in a dose-dependent manner. In a low dose, a parallel displacement to the right was observed, whereas for higher doses the shift was non-parallel. A high dose of tetrandrine shifted the pressor response curve of the alpha 1-adrenoceptor agonist, methoxamine, only slightly to the right and did not depress the maximal response. Tetrandrine also caused a moderate rightward shift of the vasopressor effect curve of vasopressin applied i.v. Tetrandrine displayed only minor affinities for specific binding sites in rat brain membranes for [3H]-prazosin (alpha 1-adrenoceptors) and for [3H]-clonidine (alpha 2-adrenoceptors). The results obtained suggest that the hypotensive effect of tetrandrine may be related to an impairment of vasoconstrictor tone mediated by vascular postsynaptic alpha 2-adrenoceptors.

Topics: Alkaloids; Anesthesia; Animals; Antihypertensive Agents; Azepines; Benzylisoquinolines; Blood Pressure; Brain; Clonidine; Heart Rate; Hypertension; Male; Methoxamine; Prazosin; Rats; Rats, Inbred Strains; Receptors, Adrenergic, alpha; Vasopressins