No abstract

We studied the effects of histamine on perfused rabbit middle cerebral arteries in vitro. Intact and endothelium-denuded preparations were compared. Histamine caused concentration-dependent constrictions in intact vessels which were competitively inhibited by an H₁ receptor antagonist. This constriction was potentiated by either H₂-receptor blockade or endothelium denudation. The greatest potentiation was observed with intraluminal as opposed to extraluminal administration. The H₁ receptor agonist pyridylethylamine induced similar concentration-dependent constriction in intact and denuded preparations. After pre-constriction, histamine, in the presence of an H₁ receptor antagonist, dilated intact vessels to a maximum of 45.1 %, and endothelium-denuded vessels to a maximum of 22% (p < 0.02). We conclude that rabbit middle cerebral arteries possess H₁ constrictory and H₂ dilatory receptors, and that many of the H₂ dilatory receptors are situated on the endothelial cells.

The muscarinic sites in arachnoid and pial vessels were compared by analysis of the binding of quinuclidinyl benzilate (QNB) to membrane preparations. Saturation analysis indicated that the process was saturable, high affinity, and related to protein concentration in both structures. Although the affinities in the two structures [KD = 0.039 (arachnoid) and 0.097 nM (pial vessels)] were similar, the arachnoid had approximately 10-fold more binding sites (Bmax = 2,100 fmol/mg of protein) than the pial vessels (Bmax = 250 fmol/mg of protein). This difference was found in both bovine and porcine fractions. Pharmacological analysis of [3H]QNB displacement by muscarinic and nonmuscarinic ligands gave the typical pattern of muscarinic receptors in both structures. Inhibition of binding to pial vessels by the M1 antagonist pirenzepine revealed only one low-affinity site (Ki = 7.8 x 10(-7) M), whereas, the arachnoid had a small proportion (21%) of high-affinity sites (Ki = 2.2 x 10(-9) M) associated with low-affinity sites (Ki = 5.50 x 10(-7) M). It is concluded that muscarinic-mediated effects that do not involve the M1 subtype are induced in bovine pial vessels by a relatively low concentration of binding sites. The high content of muscarinic binding sites and their diversity in the arachnoid suggest a functional role for muscarinic cholinergic receptors in this structure.