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Dopamine, Bromocriptine and Apomorphine produce arterial hypotension in the rat, but so far remains to be established if the phenomenon takes place at the presynaptic or postsynaptic nerve terminal. Present study deal with the locus of action of these substances. Rats were anesthetized with urethane i.p. and heparinized, maintaining the spontaneous pulmonary ventilation through a tracheal cannula. EKG and intracarotid mean blood pressure were recorded through a polygraph. Dopamine as well as Bromocriptine (3.12 to 25 mu/100 g both) and Apomorphine (0.125 to 4.0 micrograms/100 g) caused a dose-related hypotension, together with moderate bradycardia and in Apomorphine treated rats, atrioventricular block. In 28 animals, chemical sympathectomy was performed with 6-OH-DA (3 mg/100 g i.p.) and 2 hours later the three substances were injected. Under these conditions, Dopamine raised the blood pressure (p less than 0.001) while Apomorphine lessened the hypotensive effect (p less than 0.02) and Bromocriptine caused no changes on this regard. It is suggested that the main effect of Dopamine on blood pressure lies at a prejunctional nerve terminal level whereas Bromocriptine acts at the effector organ post junctional level. In Apomorphine effect it might be mainly involved a prejunctional component.

Angiotensin II induced a dose-related increase in the amplitude of contraction of preparations of isolated atria and aortic strip of rabbit. These effects were significantly higher in organs obtained from reserpine pretreated animals (4 mg/kg i.p. 24 hr before experiments) than in controls. After reserpine, the effect of four doses of angiotensin II on the blood pressure of rabbits under pentobarbital anesthesia was also significantly higher than in untreated controls.

Six-MP and its palladium and platinum complexes of this compound were administered intraperitoneally to 28 day old Sprague-Dawley rats in dosages of 15 mg/kg, 26.85 mg/kg, respectively for 21 days. The leukopenia induction capacity of 6-MP was greater at the end of day 7 while the 6-MP-Pd complex evidenced a more drastic leukocyte reduction at the end of day 21. The platinum complex was less toxic, as demonstrated by greater weight gain, while treatment with the palladium complex resulted in approximately the same weight gain as that observed in rats treated with pure 6-MP.

Copper's role in connective tissue is linked to the enzyme lysyl oxidase. From a biochemical perspective, copper is a cofactor for the enzyme and a determinant of its activity in connective tissues. Lysyl oxidase catalyses a post-translational oxidation of certain lysine and hydroxylysine residues. The peptidyl aldehydes so formed become active centres for the formation of cross-links in collagen and elastin. Less well understood is how copper controls the steady-state activity of lysyl oxidase; the enzyme fails in copper deficiency. Giving copper to a deprived animal increases lysyl oxidase activity in aortic tissue. Such activation in vivo appears to require caeruloplasmin. Suspending aortic tissue in a copper-enriched growth medium also activates lysyl oxidase provided that tissue structure is kept intact. Activation in vitro occurs with the binding of copper to a large-molecular-weight component, presumably the enzyme. Binding will not occur if protein synthesis is blocked. These studies clearly show that the synthesis of mature elastin and collagen can be controlled by the availability of copper. They further suggest that transport of copper to aortic tissue and its engagement to lysyl oxidase are linked to the synthesis or lysyl oxidase, an extracellular carrier, or both.