n 5 8 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



' — 



MAGNESIUM 



SMALL VESSEL 



SMALL 



VESSEL 



r 



-VFNOUS 



O O Jj? O O ro to O O 



§600 666-0 



INFUSION RATE ml/mm 



fig. 10. Average effect of 10% CaCU or io f c MgS0 4 

 infused into the brachial artery on dog forelimb vascular 

 resistances. [Graph prepared from tabular data in Haddy 

 (101).] 



Ca from the medium causes a dissociation of the con- 

 tractile mechanism from action potentials in the 

 guinea pig taenia coli. From this, Axelsson & Biil- 

 bring (6) have concluded that Ca is essential for the 

 activation of the contractile mechanism by action 

 potentials. Hurwitz et al. (121) have shown this in 

 another equally direct way. They observed that pro- 

 longed exposure of the guinea pig ileum to a calcium- 

 free environment divests the tissue of its ability to 

 contract in the presence of an appropriate chemical 

 stimulus. Further, the substitution of Mg for Ca in 

 the medium accelerates the loss of contractility. Even 

 so the membrane processes governing ionic exchanges 

 still function so that a stimulus which no longer causes 

 contraction will still cause K efflux 



Zsoter & Szabo (216) have reported that the 

 feeding of a high calcium diet to rats for 10 to 15 weeks 

 causes an increased sensitivity of the mesoappendix to 

 the topical application of epinephrine. As we have 

 discussed earlier, however, this type of result is 

 difficult to interpret, since the variable (calcium 

 feeding) is so remote from the target. Much more re- 

 vealing is the observation of Haddy who showed that 

 the infusion of hypertonic calcium salts caused con- 

 striction of all segments of the peripheral vascular bed 

 of the dog forelimb under conditions of controlled 

 flow (101 ). It will be recalled that hypertonic solutions 

 in general produce vasodilatation so that the result 

 with calcium is particularly striking. In a later study 

 Overbeds & Haddy (156) reported that while the 

 infusion of isotonic KC1 produced peripheral vasodila- 

 tation, isotonic CaCl 2 caused vasoconstriction. 



Woolley (213) has suggested that serotonin acts 

 directly on the cell membrane to transfer calcium 

 from the exterior to the interior of the cell. His evi- 

 dence is quite incomplete, however, and a similar 

 argument could be developed with equal reason to 

 suggest that most if not all smooth muscle-contracting 

 agents act through some similar mechanism involving 

 calcium. 



Magnesium 



Haury (105) has clearly demonstrated that Mg 

 relaxes bronchial smooth muscle and opposes the 

 action of stimulating drugs. In well-controlled experi- 

 ments in the dog and frog he found that small 

 amounts of Mg given intravenously produced a blood 

 pressure fall which was in large part due to peripheral 

 vasodilatation (106). Schmid et al. (174) carried out a 

 careful hemodynamic study in conscious dogs and also 

 concluded that Mg salts produce peripheral vasodila- 

 tation as Hoff et al. (115) had earlier claimed. Stan- 

 bury (187) emphasized that the action of Mg is com- 

 plex, since it produces changes in the autonomic 

 nervous system and the heart as well as the peripheral 

 vasculature. Zadina & Kriz (215) claimed that Mg 

 had a direct relaxing effect on the isolated guinea pig 

 intestine and depressed the response to stimulating 

 agents. 



Engbaek (59) reviewed the subject in 1952 and 

 concluded that although it seemed reasonably certain 

 that Mg ions acted to relax peripheral blood vessels 

 this had not yet been shown to be a direct effect. 



Pending any evidence to the contrary it seems 

 reasonable to conclude, in summary, that Ca causes 

 peripheral vasoconstriction and Mg relaxation. In 

 general, these actions do not appear to be in any 

 way specific to vascular smooth muscle. The special 

 role of these bivalent metal ions in the chemistry of 

 contractile protein may be involved and both ions, or 

 at least Ca, may link membrane phenomena to the 

 contractile mechanism. 



ROLE OF H + AND OH - IN VASCULAR 

 SMOOTH MUSCLE TENSION 



This subject is in a highly unsatisfactory state and 

 permits no real conclusions other than that the pH of 

 the medium is a most important variable, as we might 

 have guessed. At this stage in the investigation of ions 

 most workers are more concerned with maintaining 



