Several beneficial effects are ascribed to Allium sativum (garlic), for example, lowering of the arterial blood pressure as well as an inhibition of arteriosclerotic vascular changes(2). We investigated the influence of aqueous garlic extract and its constituents allicin, ajoene, and y-glutamylpeptides on the electro-mechanical characteristics of human coronary vessels originating from heart transplantations.

In isolated vascular strips, garlic affected the membrane potential and the mechanical force development in aqueous extracts from 0.0002-0.2 g powder/1(Kwai, Lichtwer Pharma GmbH, Berlin) (1,3). Starting from 0.0002 g/l, a stepwise increase in concentration hyperpolarized the membrane of the vascular smooth muscle cells and simultaneously reduced their contractile tone in a concentration-dependent manner (Fig. 1). The membrane potential intracellularly recorded amounted to -60.2 mV, and the maximal hyperpolarization of the cells to 2.1 mV. With a mechanical steady- state pretension of the muscle segments of 1.423 g, the maximal relaxation was 0.285 g (20% of the initial tone). Half-maximal effect on membrane potential and wall tension was obtained by a garlic extract concentration of 1.15mg/1. A therapeutic single dose of 300mg garlic powder corresponds to an extract concentration in humans of 0.882 mg/1 in the total extracellular space when assuming a 5% resorption of the garlic constituents. Therefore, the effect on membrane potential and coronary vascular tone was found in a concentration range relevant for man.

Only 0.882 mg/1 extract concentration hyperpolarizes the smooth muscle cell membrane by = -0.6 mV. With a membrane resting potential of V= -60.2 mV and a K+ equilibrium potential of Ek = -89.7 mV, 0.6 mV hyperpolarization correlates with an increase of the total membrane conductance by 10.4 pS or 3.1%. The K+ conductance rises from 335.6 pS to 345.9 pS which corresponds to an augmentation of the K+ channel open probability of Popen(K+) = 0.00034 tp 0.00035 underlying 50,000KCa channels per cell with a single channel conductance of 20 pS. At the resting potential 17K+ channels are opened, after application of a single dose of 300 mg garlic powder 18 K+ channels. Simultaneously, the membrane hyperpolarization of 0.6 mV reduces the L-type Ca2+ channel open probability of Popen(Ca2+) = 0.00195 to 0.00179, i.e. by 8.2%. A open of -0.00016 diminishes the number of open Ca2+ channels from 4 to 3. The Ca2+ inward current into the vascular smooth muscle cells decreases by 7.9%, relaxation is the consequence.

Comparing these effects with those of the garlic compounds allicin and ajoene, one obtains a similar course in membrane potential and wall tension for aqueous solutions in concentrations between 10-9 and 10-6 mol/1 (2,3). Cumulative 15-minute application of allicin hyperpolarized the membrane of the vascular smooth muscle cells by maximally 5.1 mV, and reduced the tone by 0.361 g (24% of the initial tone). Half-maximal effect appeared at a concentration of 6.2 x 10-9 mol/1 allicin. In principle equal changes, although diminished, occurred under ajoene in the same concentration range. Ajoene caused a membrane hyperpolarization of maximally 4.4 mV with simultaneous relaxation of 0.166 g (11% of the initial tone). The EC50 value for ajoene amounted to 9.9 x 10-9 mol/1.

On the other hand, opposing effects were produced with a y- glutamylpeptide fraction. When dialysing aqueous garlic extract by ultra filtration (filtration limit about 1 kD), one obtains a peptide fraction that neither incorporates allicin and ajoene nor other compounds with a molecular mass < 1 kD. This aqueous extract of y- glutamylo-ligopeptides from 0.0002-0.2g garlic powder/1 caused a concentration-dependent membrane depolarisation of maximally 6.1.mV, and increased the tone by 0.235 g (15% of the initial tension). Half-maximal effect occurred at an extract concentration of y-glutamyloligopeptides from 0.00223 g garlic powder/1. Thus, the depolarising and vasoconstrictor influences of the y--glutamyloligopeptides counteract the hyperpolarizing and vasodilatory effects of allicin and ajoene, although the latter predominate.

A linear-quantitative calculation based upon the single effects yields that for each garlic extract concentration tested the dilatation measured in the whole extract results exactly from the sum of the relaxing and contracting effects of the individual garlic constituents. Therefore, allicin and ajoene together dilate more strongly than the y-glutamyloligopeptides constrict. The same relationships hold for the individual depolarising and hyperpolarizing influences, respectively, so that the total extract finally exerts a hyperpolarizing effect on the vascular smooth muscle cell membrane.