Normal dogs were injected i.v. with 0.25 mg/kg sodium salt of HB 419 (glibenclamide) and plasma insulin concentrations were measured over a period of 2 hrs. When the animals were given a single i.v. injection of 0.2 mg/kg dihydroergotamine tartrate (DHE) 30 min prior to the administration of HB 419, the insulinogenic effect of the sulfonylurea was considerably amplified (192 muU/ml vs 34 muU/ml at 45 min). No augmentation of the insulinogenic effect of HB 419 was observed when the same experiments were conducted with 0.05, 0.025 or 0.01 mg/kg ergotamine tartrate. At the dose level of 0.1 mg/kg the insulinogenic effect of HB 419 was suppressed. Since the structural difference between these two ergot alkaloids consists of the presence or absence of the double bond at C9 and C10 of the lysergic acid moiety, it appears that saturation of this double bond is an essential structural requirement for DHE to function as an amplifier of sulfonylurea-stimulated insulin release.

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PubMedDate not supplied

The effect of glucagon on the glycosaminoglycan content of canine arteries.

Hypophysectomized young beagles were treated for 21 days with pharmacological doses of glucagon, administered intramuscularly in two daily injections of 0.5 mg each. Hyaluronic acid, heparan, dermatan and isomeric chondroitin sulphates were determined in aorta, carotid, iliac, renal, mesenteric and coronary arteries. In comparison with age-matched hypophysectomized controls, glucagon-treated dogs showed a reduction in the heparan sulphate concentration in their carotid arteries and thoracic aorta. These results indicate that glucagon has a very limited effect on arterial glycosaminoglycan content.

Animals↗

PubMedDate not supplied

The relationship of hormones to arterial glycosaminoglycans and atherosclerosis.

Glycosaminoglycan fractions were measured in representative large and medium sized arteries of normal, hypophysectomized and hormone treated young beagles. Hyaluronate, heparan sulphate, dermatan sulphate and the isomeric chondroitin sulphates were determined in the aortic arch, thoracic and abdominal segments, in the external iliac, superior mesenteric, renal, common carotid and coronary arteries. The hormones used for replacement therapy of hypophysectomized animals were growth hormone, thyroxine, cortisone and the sex hormones testosterone, estrogen and progesterone. The sensitivity to an individual hormone was found to differ in various segments of the arterial tree; the thoracic and abdominal aorta were most responsive but renal and superior mesenteric arteries were relatively inert. The hypothesis is advanced that arteries with a GAG metabolism highly sensitive to hormones are more prone to develop atherosclerosis than arteries that have a limited sensitivity to alterations in endocrine balance.

Animals↗