Vasodilator activity of human alpha-calcitonin gene-related peptide in the feline mesenteric vascular bed.

Human alpha-calcitonin gene-related peptide (CGRP) is a substance immunohistochemically present in a number of organ systems; however, the biologic significance of this peptide is uncertain. The present study was undertaken to investigate the effects of CGRP in the feline mesenteric vascular bed under conditions of controlled blood flow. Bolus injections of CGRP decreased mesenteric perfusion pressure in a dose-related fashion. When compared with nitroglycerin, CGRP possesses markedly greater vasodilator activity in the intestinal vascular bed of the cat. Because circulating levels of CGRP have been identified, the present data suggest CGRP may play a role in the regulation of systemic vasomotor tone and regional hemodynamics, as well as involve altered calcium metabolism seen with other calcium-regulating hormones in hypertensive states.

Influence of SQ 29,548 on vasoconstrictor responses in the mesenteric vascular bed of the cat.

The effects of SQ 29,548 on vasoconstrictor responses were investigated in the feline mesenteric vascular bed. Injections of the thromboxane (TX) A2 mimics, U46619 and U44069, caused dose-related increases in mesenteric arterial perfusion pressure. After administration of SQ 29,548, 0.5 mg/kg i.v, vasoconstrictor responses to U46619 and U44069 were reduced markedly whereas responses to prostaglandin (PG) F2 alpha, angiotensin II, vasopressin and BAY K 8644, an agent which enhances calcium entry, were not altered. The duration of the TXA2 receptor blockade was greater than 2 h and SQ 29,548 had no significant effect on mesenteric vasodilator responses to PGE2, isoproterenol, nitroglycerin, acetylcholine or bradykinin. SQ 29,548, at a dose of 0.5 mg/kg i.v., significantly reduced the response to TXB2, which had modest vasoconstrictor activity in the mesenteric vascular bed. However, when the dose of SQ 29,548 was reduced to 0.05 mg/kg i.v., responses to TXB2 were not altered, whereas responses to U46619 were significantly decreased. SQ 29,548 had no significant effect on vasoconstrictor responses to norepinephrine or to sympathetic nerve stimulation. The TXA2 receptor antagonist blocked the vasoconstrictor component of the biphasic response to the PG precursor, arachidonic acid, and the endoperoxide, PGH2. The results of these studies suggest that SQ 29,548 is a specific TX receptor antagonist in the mesenteric vascular bed, that the vasoconstrictor component of the biphasic response to arachidonic acid and PGH2 is due to formation of TXA2, and that endogenously formed TXA2 does not modulate adrenergic responses in the mesenteric circulation of the cat.

Protective action of zinc against cobalt-induced testicular damage in the mouse.

The purpose of this study was to determine if toxic effects of cobalt on the murine testis could be prevented by zinc, an essential metal for spermatogenesis. CD-1 male mice were administered one of the following in their drinking water: 1) 400 ppm CoCl2, 2) 800 ppm ZnCl2, 3) 400 ppm CoCl2 + 800 ppm ZnCl2, or 4) distilled water. After 13 weeks, animals were sacrificed and testes were excised, weighed, and processed for histologic study. Comparison of testicular weights revealed no difference between the control and zinc-treated groups, while there was a small but significant reduction in the zinc/cobalt-treated group, and a large reduction in the cobalt-treated group. Histologic evaluation of testes confirmed the degenerative effects of cobalt, as well as the normal morphology in the zinc-treated group. Furthermore, 90% of the animals in the zinc/cobalt-treated group exhibited complete or partial protection as demonstrated by tubular morphology. This study indicates that zinc prevents cobalt-induced testicular damage.