15.11. 1976

Specialia

No c h a n g e s in t h e levels of n o n - e s t e r i f i e d f a t t y acids a n d a m i n o a c i d n i t r o g e n levels in blood s e r u m were found. All C H E r e a c t i v a t o r s increase t h e secretion of corticosterone. This effect reaches s t a t i s t i c a l significance w i t h methoxim and obidoxim. A f t e r e p i n e p h r e c t o m y , C H E r e a c t i v a t o r s no longer e v o k e d an increase in glycogen c o n c e n t r a t i o n in h e a r t muscle, b u t r a t h e r a t r e n d t o decrease was seen, b u t t h i s c h a n g e was n o t s i g n i f i c a n t (Table).

Glycogen concentration in heart muscle from normal and epinephrectomized rats 2 h after administration of drugs (20 mg/kg s.c.)

Normal rats

Epinephrectomized rats

Treatment

n

rag/100 g su

n

rag/100g

s;

Saline Trimedoxim Methoxim

43 11 21 14

279.9 334.0 354.7~ 419.9~

4 5 4 5

235.2 201.4 157.4 166.2

36.4 38.2 23.9 18.2

Obidoxim

13.1 29.8 15.8 23.47

~Statistically significant difference from control values (saline); p < o.01.

1447

Discussion. Our p r e v i o u s p a p e r (BENEgOV-~ a n d H v l z DOgOV~ 1) d e m o n s t r a t e d clearly t h a t C H E r e a c t i v a t o r s can induce a n increase in glycogen c o n c e n t r a t i o n in liver, skeletal a n d h e a r t muscle, a n d a n increase in blood glucose level in rats. The first series of e x p e r i m e n t s conf i r m e d again t h e rise of glycogen in muscle. I f a rise in liver a n d muscle glycogen a p p e a r s s i m u l t a n e o u s l y w i t h t h e rise of g l y c a e m i a in h u n g r y animals, t h e m o s t p r o b able e x p l a n a t i o n is glnconeogenesis. The a c t i v a t i o n of a d r e n a l c o r t e x a n d increased release of c o r t i c o s t e r o n e o b s e r v e d s u p p o r t t h i s h y p o t h e s i s . T h e lack of muscle glycogen rise in e p i n e p h r e c t o m i z e d a n i m a l s m a y repres e n t f u r t h e r e v i d e n c e for t h i s conclusion. F u r t h e r findings - u n c h a n g e d levels of n o n - e s t e r i f i e d f a t t y acids a n d of a m i n o acid n i t r o g e n - n e e d n o t be in c o n t r a d i c t i o n , since t h e t u r n o v e r of a m i n o acids released f r o m p r o t e i n s a n d f a t t y acids f r o m fats m a y be a t s u c h a speed t h a t no c h a n g e in t h e s e m e t a b o l i t e s levels is d e t e c t a b l e . The e s t i m a t i o n of c a t e c h o l a m i n e s in adrenals, revealing a fall in c o n c e n t r a t i o n a f t e r t h e a d m i n i s t r a t i o n of C H E r e a c t i v a t o r s i n d i c a t e s also slight a c t i v a t i o n of t h e a d r e n a l medulla. The lack of a n y c h a n g e in t h e a c t i v i t y of liver t r y p t o p h a n e - p y r r o l a s e and v a r y i n g effects of C H E react i v a t o r s on t h e release of a d r e n a l c a t e e h o l a m i n e s (decrease of n o r a d r e n a l i n e a f t e r m e t h o x i m a n d t o x o g o n i n , decrease of a d r e n a l i n e a f t e r t r i m e d o x i m ) is s t i l l d i f f i c u l t to explain.

A c t i v a t i o n of S u s t a i n e d S y m p a t h e t i c V a s o d i l a t a t i o n i n D o g b y S p i n a l C o r d S t i m u l a t i o n 1 T. F. ROLEWICZ ~ a n d B. G. ZIMMERMAN

Department o/Pharmacology, University o/ Minnesota, 105 Milliard Hall, Minneapolis (Minnesota 55d55, USA), 31 May 1976. Summary. E l e c t r i c a l s t i m u l a t i o n in lateral sites of t h e u p p e r cervical spinal cord evoked v a s o d i l a t a t i o n after adrenergic blockade. S y m p a t h e t i c fibres m e d i a t i n g s u s t a i n e d v a s o d i l a t a t i o n were s h o w n to be s e p a r a t e f r o m a d r e n e r g i c s y m p a t h e t i c fibres since t h e a d r e n e r g i c v a s o c o n s t r i c t o r r e s p o n s e in t h e p a w e v o k e d b y v a s o m o t o r s t i m u l a t i o n ill t h e medulla was n o t r e v e r s e d to v a s o d i l a t a t i o n a f t e r b r e t y l i u m . A v a s o d i l a t o r i n n e r v a t i o n w h i c h can be a c t i v a t e d b y s y m p a t h e t i c s t i m u l a t i o n following adrenergic b l o c k a d e exists in t h e c u t a n e o u s v a s c u l a t u r e of t h e canine p a w a and ear* a n d in t h e h i n d l i m b 5. T h e v a s o d i l a t a t i o n b r o u g h t a b o u t b y s t i m u l a t i o n of t h e s e s y m p a t h e t i c fibers is in p a r t m e d i a t e d b y a c e t y l c h o l i n e since t h e initial r a p i d l y d e v e l o p i n g c o m p o n e n t of t h e r e s p o n s e is b l o c k e d b y a t r o p i n e 5. The m a j o r i t y of t h e response, h o w e v e r , w h i c h is of long d u r a t i o n is n o t a t t r i b u t a b l e to cholinergic m e d i a t i o n or to release of o t h e r k n o w n t r a n s m i t t e r s a, 5 a n d h a s been t e r m e d s u s t a i n e d v a s o d i l a t a t i o n 5. B e c a u s e it is of i m p o r t a n c e to k n o w w h e t h e r c e n t r a l r e p r e s e n t a t i o n of t h i s u n i q u e v a s o d i l a t o r s y s t e m exists, s t i m u l a t i o n of t h e lateral a s p e c t of t h e u p p e r cervical spinal cord was e x p l o r e d as a m e a n s of a c t i v a t i n g s u s t a i n e d v a s o d i l a t a tion. E x p e r i m e n t s utilizing m e d u l l a r y v a s o m o t o r c e n t e r s t i m u l a t i o n were also c o n d u c t e d to t r y to s e p a r a t e p h y s iologically t h e a d r e n e r g i c a n d s u s t a i n e d v a s o d i l a t o r innervarious. Materials and methods. E x p e r i m e n t s were carried o u t in 19 m o n g r e l dogs a n e s t h e t i z e d w i t h 30 m g / k g of s o d i u m p e n t o b a r b i t a l a n d artificially v e n t i l a t e d a f t e r a d m i n i s t r a t i o n of 0.25 m g / k g of d e c a m e t h o n i u m b r o m i d e . Supplem e n t s of t h e a n e s t h e t i c a n d n e u r o m u s c u l a r blocker were given w h e n necessary. W i t h t h e a n i m a l in t h e p r o n e posit i o n a n d its h e a d placed in a holder, t h e m e d u l l a a n d up-

p e r m o s t p o r t i o n of t h e cervical spinal cord were exposed t h r o u g h an incision over t h e c i s t e r n a m a g n a . A bipolar c o n c e n t r i c electrode was used to s t i m u l a t e either t h e m e d u l l a (floor of t h e 4 t h ventricle) or t h e l a t e r a l spinaI cord. Various sites 1-6 m m below t h e floor of t h e 4th v e n t r i c l e a n d on t h e lateral a s p e c t of t h e spinal cord j u s t c a u d a l to t h e m e d u l l a 1-2 m m b e n e a t h t h e surface were s t i m u l a t e d . T h e p r o c e d u r e of h i n d p a w p e r f u s i o n w h i c h h a s b e e n r e p o r t e d p r e v i o u s l y a e n t a i l e d p u m p i n g blood f r o m t h e f e m o r a l a r t e r y t o t h e cranial tibial a r t e r y of t h e left h i n d p a w w i t h a S i g m a m o t o r p u m p . T h e e x t r a corporeal t u b i n g e n c o m p a s s e d 75 ml a n d i n c l u d e d a 53 ml coil w h i c h d e l a y e d t h e passage into t h e paw" of catechola m i n e s released f r o m t h e a d r e n a l m e d u l l a d u r i n g central elicitation of v a s o d i l a t o r responses. The a n i m a l was p r i m e d i.v. w i t h 75 m l of 5% d e x t r a n to replace t h e blood

J Supported by USPHS Grant No. HL 08570 and part of thesis work by Dr. ROLEWleZ. Address: Department of Pediatrics, St. Pmfl Ramsey Hospital, St. Paul, Minnesota, USA. a B. G. ZIMMERMA~r J. Pharmae. exp. Ther. 152, 81 (1966). a T. F. ROLEWlCZ and B. G. ZIMMERMAN, Am. J. Physiol. 223, 939 (1972). 5 L. BECK, A. POLLARD, S. O. KAYAALP and L. M. WEINER, Fed.

Proc. 25, 1596 (1966).

1448

Specialia

t a k e n u p b y t h e e x t r a c o r p o r e a l t u b i n g . I n o r d e r to v a s c u l a r l y isolate t h e p a w d u r i n g c e n t r a l s t i m u l a t i o n , a ligature p l a c e d a r o u n d t h e a o r t a e x p o s e d t h r o u g h a ret r o p e r i t o n e a l incision was t i g h t e n e d prior to s t i m u l a t i o n . This p r e v e n t e d p a s s a g e of a n y v a s o c o n s t r i c t o r s u b s t a n c e s in t h e s y s t e m i c c i r c u l a t i o n f r o m r e a c h i n g t h e p a w via collateral arteries. S y s t e m i c blood p r e s s u r e a n d p a w p e r fusion p r e s s u r e were m o n i t o r e d f r o m s i d e - a r m s in t h e p e r f u s i o n t u b i n g p r o x i m a l a n d distal to t h e p u m p , respectively. P r e s s u r e s were m e a s u r e d w i t h S t a t h a m t r a n s ducers c o u p l e d to a B e c k m a n d y n a g r a p h . F l o w was initially a d j u s t e d to set p e r f u s i o n p r e s s u r e a t a p p r o x i m a t e l y t h e level of s y s t e m i c blood pressure a n d was m a i n t a i n e d c o n s t a n t t h r o u g h o u t t h e e x p e r i m e n t s . The left l u m b a r s y m p a t h e t i c t r u n k was e x p o s e d t h r o u g h a r e t r o p e r i t o n e a l incision so t h a t it could also be s t i m u l a t e d . P a r a m e t e r s of s t i m u l a t i o n were 10 V, 0.5-1 msec a n d 7-20 H z for t h e s y m p a t h e t i c t r u n k , 5-10 V, 0.5 msec a n d 120 H z for t h e spinal cord a n d 20 V, 0.5 msec a n d 240 H z for t h e medulla. V a s o d i l a t o r r e s p o n s e s were e x p r e s s e d as a p e r c e n t a g e of t h e c o n t r o l p e r f u s i o n p r e s s u r e (PP) w h i c h was c o n s i d e r e d as 100%. The p a i r e d t-test was e m p l o y e d to d e t e r m i n e s t a t i s t i c a l differences. Results. P r i o r to s t i m u l a t i n g t h e left lateral spinal cord, b r e t y l i u m , 10 15 m g / k g a n d a t r o p i n e sulfate, 0.25 m g / k g were a d m i n i s t e r e d to abolish adrenergic a n d cholinergic r e s p o n s e s t o s y m p a t h e t i c n e r v e s t i m u l a t i o n . T h e left l u m b a r s y m p a t h e t i c n e r v e was s t i m u l a t e d a t 20 H z for

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Activation of sustained sympathetic vasodilatation in dog by spinal cord stimulation.

15.11. 1976 Specialia No c h a n g e s in t h e levels of n o n - e s t e r i f i e d f a t t y acids a n d a m i n o a c i d n i t r o g e n levels...
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