Medial smooth-muscle cell lesions and dissection of the aorta and muscular arteries.

We report a case of aortic, coronary, and renal artery dissections associated with pregnancy. The histologic changes related to the hemorrhages included smooth-muscle cell (SMC) proliferation with fibrosis, elastin fragmentation and collagen degeneration, and SMC vacuolar degeneration and coagulation necrosis. These lesions seemed to be prototypes for dissection, since they were associated with aortic and muscular artery dissections in three additional cases unrelated to pregnancy. In each case, dissections seemed to result from SMC activity that also involved the systemic vasculature, veins, and visceral smooth muscle in histologic patterns that could be explained as a product of SMC metabolism. We propose that the histologic changes associated with dissections are best explained as a product of the metabolism of SMCs that function as multifunctional mesenchyma in a manner controlled by variable penetrance of a gene that controls their metabolism.

Binding of the A1-selective adenosine antagonist 8-cyclopentyl-1,3-dipropylxanthine to rat brain membranes.

8-Cyclopentyl-1,3-dipropylxanthine (PD 116,948) is a very potent, very A1-selective adenosine antagonist, with a Ki of 0.46 nM in 3H-CHA binding to A1 receptors in rat whole brain membranes and 340 nM in 3H-NECA binding to A2 receptors in rat striatal membranes. Its 740-fold A1-selectivity is the highest reported for an adenosine antagonist. 3H-PD 116,948 (117 Ci/mmol) was prepared by reduction of the diallyl analog. 3H-PD 116,948 bound to a single site in rat whole brain membranes, with a Bmax of 46 pmol/g wet weight and Kd of 0.42 nM. Nonspecific binding was extremely low, amounting to about 3% of total binding under standard conditions and less than 1% when higher tissue concentrations were used. Affinities of compounds for inhibition of 3H-PD 116,948 binding were highly consistent with an A1 adenosine receptor. Antagonists were equally potent in 3H-PD 116,948 binding and in 3H-CHA binding, while agonists were consistently about 12-fold more potent in 3H-CHA binding. Hill coefficients were 1.0 for antagonists and about 0.65 for agonists. 3H-PD 116,948 should be a useful antagonist ligand for adenosine A1 receptors.

Structural changes within the media of coronary arteries related to intimal thickening.

From observations on 454 coronary arteries from subjects ranging in age from prematurely newborn to 90 years, six structural patterns of medial smooth muscle are interpreted as representing, or related to, the proliferation and/or migration of medial smooth muscle into intima. By measuring the extent of inner medial circumference occupied by four of the six patterns, it was possible to calculate a numerical value designated the medial proliferatice and / or migratory activity (MP-MA) of each artery. During the first three decades, nonatherosclerotic diffuse intimal thickening was the characteristic intimal process, and during this phase of the arterial maturation span, the MP-MA of the arteries was significantly related to the degree of intimal thickening. Following a peak MP-MA level by the end of the third decade, there was a progressive decrease in the MP-MA level as the incidence and severity of atherosclerotic intimal thickening increased. At advanced stages of atherosclerotic intimal thickening, which were associated with thinning of adjacent media, intimal-medial structural patterns indicating a relationship between medial smooth muscle proliferative activity and the expanding atherosclerotic plaque were also apparent. The observations support the concept that the movement of medial smooth muscle into intima is a critical step preceding and during the evolution of the atherosclerotic plaque.