The existence of β-receptors and their possible contribution to the vascular tone of pial arteries was investigated using the microapplication technique combined with the measurement of vascular diameter. Concentration response curves for (+) and (−)propranolol revealed an identical course with no vascular reaction occurring between 2.5×10−10 and 2.5×10−5 M propranolol. Since both (+) and (−)propranolol were without effect on vascular diameter over a wide concentration range it is concluded that the vascular tone is not influenced by β-receptors under these experimental conditions. The increase in vascular diameter (60%) observed at 2.5×10−4 M (+) and (−)propranolol is supposed to be due to an unspecific effect. Concentration response curves for isoproterenol revealed no vascular reaction between 2.5×10−11 and 2.5×10−8 M, dilations of 4–5% at 2.5×10−7 and 2.5×10−6 M, constrictions of about 5% at 2.5×10−4 and of 3% at 1.25×10−3 M isoproterenol. These weak vascular reactions cannot be explained by reduced biological activity of isoproterenol due to autoxidation during storage. It is concluded that β-receptors are of little or no physiological significance for regulation of the vascular tone of pial arteries.

The effect of perivascular osmolarity on the diameter of pial arteries was studied in cats by the microapplication technique. Between 251 and 360 mosmoles/liter, concentration-response curves were obtained for single vessels. Constriction occurred when perivascular osmolarity was decreased below 317 mosmoles/liter, and dilation occurred at osmolarities above this value. The effect was the same whether the osmolarity was changed by addition of mannitol or NaCl. Reduction of sodium concentration from 156 to 133 mEq/liter at constant osmolarity did not affect arteriolar diameter, but greater reductions in sodium concentration induced vasoconstriction. The results indicate that the resistance of pial arteries can be influenced by local changes in perivascular osmolarity.

The effects of and the interaction between local perivascular variation in potassium and bicarbonate concentration on the diameter of pial arteries were studied in cats by the microapplication technique. At 11 mEq/liter of bicarbonate, a direct correlation existed between vascular diameter and K + concentrations between 0 and 10 mEq/liter. At K + concentrations between 10 and 20 mEq/liter, no further increase in vascular diameter was observed. At a K + concentration of 5 mEq/liter, an inverse relationship existed between pial arterial diameter and perivascular bicarbonate concentrations between 0 and 22 mEq/liter. At K + concentrations of 0 and 10 mEq/liter, the pial arterial diameter was determined strongly by the K + concentration and was only slightly, if at all, influenced by bicarbonate concentrations between 5 and 22 mEq/liter. At lower bicarbonate concentrations the local acidity induced a marked vasodilation. The results indicate that the diameter of pial arterioles in cats is affected by periarteriolar concentrations of K + and H + ; the degree of the vasoreaction induced by H + is modulated by K + .

The influence of norepinephrine on the diameter of single pial arteries and arterioles was investigated by adding the drug to the perivascular space with micropipettes. The mock spinal fluid solution in which the norepinephrine was dissolved contained 0, 11, or 22 mEq/liter of bicarbonate. These concentrations of bicarbonate were by themselves found to dilate, cause no change, and constrict the pial vessels, respectively. Concentration-response curves with 11 mEq/liter of bicarbonate over the concentration range of 5 x 10 -4 to 5 mmoles/liter of norepinephrine showed significant constriction at 5 x 10 -2 mmoles/liter and maximal constriction (40% of diameter) at 2.5 mmoles/liter. In bicarbonate-free solution, the slope of the concentration-response curves was less, and at 22 mEq/liter of bicarbonate norepinephrine had no effect. The pial arteries seemed to be less sensitive than the mesenteric and the cremasteric arteries to norepinephrine. The present data demonstrate the existence of norepinephrine receptors on the pial arterial smooth muscle cells, which satisfies the major requirement for the possible existence of a sympathetic control of cerebral blood flow.

The significance of catecholamines in the regulation of cerebral vessel resistance to blood flow was investigated by means of the perivascular space of pia arteries and arterioles of the cat. The local perivascular application of catecholamines is particularly suitable for this investigation, since vascular reactions can be detected independently of any changes in systemic hemodynamics, metabolism and acid base status.The method also excludes the modifying effect of the blood brain barrier on intravascularly applied substances. The diameter of the vessels was measured from microphotographs taken of the cerebral surface. The catecholamines (norepinephrine and epinephrine 0.1, 1, 10, 100, 500, 1000 /ug/ml) were solved in mock spinal fluid (11.5 mEq/l HCO 3 − )after the latter was found to have little or no vascular effect.