EFFECTS OF IONS ON VASCULAR SMOOTH MUSCLE 



I 145 



the cell's ionic relation with its environment and may 

 demand an efflux of K ions; this may be the basic 

 process. This is supported by the fact that under 

 similar circumstances, responsiveness can be as well 

 restored by increasing K in the medium. In the third 

 place, as described above, hyporesponsiveness occurs 

 also in extremely low Na media when Na, must 

 necessarily be very low rather than high as after 

 stimulation. Clearly, however, a reduction in the Na 

 gradient is common to both hyporesponsive situations. 



If an increase of tension in smooth muscle is 

 ordinarily associated with a shift of Na from outside 

 to within the cell as McDowall & Zayat (145) have 

 suggested for uterine muscle and as we shall later 

 suggest is a general process, we can distinguish in this 

 the importance of the Na gradient. Thus, we (78) 

 have shown that contraction of a colon strip, induced 

 by a variety of agents, can be aborted by adding Na 

 to the medium. This procedure affects only Na„ and 

 not Na, and thus directly implicates the Na gradient 

 in the induction of the tension increase and not the 

 simple intracellular gain in Na considered alone. We 

 shall later associate these changes with K distribution 

 as well. 



There is reasonably consistent evidence concerning 

 the events following exposure of a smooth muscle 

 strip to a medium containing supranormal Na con- 

 centration. If the concentration of Na is high enough, 

 the first response appears to be an increase of tension 

 which is sustained for some minutes (10 or so) and 

 then declines to subnormal levels as equilibration 

 proceeds. This has been shown to apply to guinea 

 pig taenia coli (1 16) and to the dog aorta strip (214). 

 The increase in tension can be partially but not en- 

 tirely attributed to an increase in osmotic pressure of 

 the bathing solution. Other authors who did not raise 

 Na„ quite so extremely noted no change in tension, 

 but agree that tissues so exposed become hyporespon- 

 sive to drug stimulation. We (78) recorded such a 

 decline in reactivity of the colon strip following ex- 

 posure to even moderate elevations of Na„ . William- 

 son & Moore (aog) observed that a rise in Na and a 

 fall in K„ , either individually or in combination, 

 caused a lessened response of the isolated rabbit aorta 

 strip to norepinephrine. Similar findings were re- 

 ported earlier by Bohr et a/. (13). We cannot account 

 for the observation of an increase in responsiveness to 

 epinephrine under similar circumstances (214). 



Although the complexity of the procedures and 

 responses used to study this problem almost defy 

 rational interpretation, several fundamental facts do 

 emerge. 



/ ) Vascular smooth muscle, like other types of 

 smooth muscle, responds to sudden reduction of Na„ 

 with a temporary increase of tension proportionate to 

 the degree of change in the medium. Tension declines 

 as equilibration proceeds. 



2) After equilibration in moderately low Na 

 media, the responsiveness of vascular smooth muscle 

 is unchanged or increased. At critically low levels of 

 Na„ the tissue becomes hyporesponsive. 



3) Vascular smooth muscle exposed to high Na,, 

 may show a temporary increase in tension, but very 

 high levels of Na are required for this. 



^) After equilibration in high Na„ media the re- 

 sponsiveness of vascular smooth muscle is substantially 

 reduced. 



5 ) Studies of the effects of ions must distinguish 

 between immediate effects which reflect a temporary 

 instability and later effects which depend on the new 

 equilibrium. 



EFFECTS OF MANIPULATION OF K IN THE MEDIUM. Al- 

 though the procedures and responses vary a good deal, 

 it has been found that most types of smooth muscle 

 increase their tension upon exposure to a potassium- 

 enriched environment. The older literature has been 

 reviewed by Evans (60) and the more recent by 

 Goffart & Bacq (91). The latter authors indeed go so 

 far as to point out that the potassium-induced con- 

 traction can be used as a basic procedure for the 

 study of agents which enhance (sensibilize) or inhibit 

 the response. The following reports are typical of the 

 studies carried out and of the results obtained. 



Holman (118) studying guinea pig taenia coli 

 reported that at first a reduction of K in the medium 

 produced little effect. After a few minutes, however, 

 tension began to fall and on prolonged exposure low 

 levels were reached and maintained. 



Exposure of the uterus of the rat, guinea pig, rabbit, 

 or cat to an elevation of K in the medium produces an 

 immediate contraction (190). So, too, the intestine 

 strip shows an immediate increase in tension (3, 1 18, 

 147, 204). Cantoni & Eastman (28) observed that the 

 temporarv depression which follows maximal con- 

 traction of the guinea pig intestine exposed to hista- 

 mine, acetylcholine, pilocarpine, barium chloride, or 

 Mecholyl can be overcome by a small increase of K. 

 in the medium. Similarly, Hazard & Cornec (107) 

 found that small amounts of K increased the response 

 of the rat duodenum to acetylcholine. 



In general, vascular tissue follows similar patterns. 

 As early as 1926 Gellhorn (90) attempted to place a 

 series of cations in a rank order based on their effects 



