Influence of mannitol on contractile responses of isolated perfused arteries

The influence of hyperosmotic mannitol on vascular smooth muscle contractile responses was examined in isolated arterial preparations. Vasoconstrictor effects of norepinephrine (NE) and potassium chloride (K+) in the perfused central artery of the rabbit's ear and in perfused mesenteric arteries of cats were significantly inhibited by infusion with Krebs bicarbonate solution made hyperosmotic with mannitol (50-200 mosM increase). Similarly, the magnitude and duration of vasoconstrictor responses to transmural stimulation of the central ear artery of the rabbit were decreased by hyperosmotic mannitol (50 mosM). Mannitol (50 mosM) produced a decrease in perfusion pressure when perfusion pressure was maintained at an increased level by K+ (60 mM). Mannitol-induced vasodilatation was not affected by ethacrynic acid (1.5 X 10(-5) M), beta adrenergic blockade or by the development of tachyphylaxis to the vasodilator effects of nitroglycerin. The concentration of cyclic adenosine-monophosphate was not changed by mannitol. Isotonic mannitol also inhibited NE-induced contractile responses. These data indicate that hyperosmotic mannitol produces vasodilatation in isolated arterial smooth muscle by a mechanism(s) that appears dissimilar from that of several other vasodilator substances and suggest that hypertonicity may not be the only factor involved in the vasodilator effect of mannitol.