The canine posterior vena cava was excised and divided into three embryologically distinct segments: segment A (supradiaphragm), segment B-C (intra-hepatic and that between liver and renal veins), and segment D (infrarenal). Circular and longitudinal strips were cut from each segment, suspended in Krebs bicarbonate solution and isometric tensions were recorded. The responses to six vasoactive agents, as well as transmural neural stimulation were studied. Maximum tension and ED₅₀ were obtained for norepinephrine, epinephrine, acetylcholine, bradykinin, histamine and 5-hydroxytryptamine (5-HT). The responses were not only quantitatively, but qualitatively different among the three segments. Bradykinin constricted the strip:; in A and B-C but not in D. 5-HT (<10^–5 m) caused a dose-dependent contraction in A and D through its direct stimulating action, while in C, a contractile response appeared only after administration of a higher dose of 5-HT. This was due to an indirect sympathomimetic action of the agent. Segment B-C, which histologically contained massive longitudinal muscle bundles in the outer layer of the wall, exhibited spontaneous, rhythmic contractions. The existence of a cholinergic excitatory innervation, in addition to adrenergic, was demonstrated in C by transmural neural stimulation.

Abstract-Using isolated dog veins, we examined whether correlations exist between the regional differences in sensitivity to drugs and their embryogenesis.Twelve different veins were dissected. In the analysis, the data obtained previously for the inferior vena cava were also included. Spiral strips were prepared and the contractile responses to cumulative application of norepinephrine (NE), 5-hydroxytryptamine (5-HT), histamine (Hist) and acetylcholine (ACh) were recorded isometrically.For each drug, a histogram was drawn by stacking the overlapping ranges (mean-:_S.E.) of the pD2 value for each vein. The histogram indicated the number of veins which could share the same pD2 value. We obtained the following results: (I) Veins of the body wall had high sensitivity to NE (pD2 >6.40) and 5-FIT (pD2 --6.60) and veins of the intestinal system, except for the splenic vein, were not so sensitive to NE and 5-HT, but exhibited high sensitivity to Hist (pD2 :,>4.60), (2) the middle segment of inferior vena cava responded similarly to portal and mesenteric veins; (3) the responses of splenic vein to the agents used were quite different from those of portal and mesenteric veins. These results suggest possible correlations between the responsiveness of venous smooth muscles and embryogenesis of the venous system. Previously we reported on the regional differences of canine veins in responsiveness to bradykinin, and classified the veins into high and low sensitive groups (1). Specifically, the inferior vena cava was found to be a mosaic vessel which exhibited marked segmental differences in the response to several vasoactive substances as well as differences in the histological features (2). It was further revealed that the innervation was also entirely different among the segments of the vessel (3). In the course of these investigations, re markable correlations were noted between the regional differences and the embryogenesis of the venous system. A question arises as to whether these findings can be regarded as examples having more general implications.The present study was undertaken to obtain a wider view of the problem. Comparison based on a common, simple criterion was made among various sites of dog veins regarding their sensitivity to four vasoactive agents. The veins of the intestinal system were clearly different from those of the body wall. Some notable correlations with embryogenesis, and Present address:

The responsiveness of helical venous strips isolated from fifteen different sites in the body of dogs to relatively selective alpha 1- and alpha 2-adrenoceptor agonists was studied, as well as to a non-selective alpha-adrenoceptor agonist. Longitudinal strips of the portal and mesenteric veins and the inferior vena cava between the liver and the renal vein (segment C) were also investigated. All veins contracted to noradrenaline or phenylephrine whereas only seven veins responded significantly to clonidine: the saphenous, cephalic, jugular and femoral veins and longitudinal strips of the portal and mesenteric veins and the segment C of the inferior vena cava. The brachiocephalic, azygos, pulmonary and splenic veins and the superior vena cava and the supradiaphragmatic portion (segment A) and the infrarenal portion (segment D) of the inferior vena cava responded little to clonidine. Unlike the longitudinal strips, the helical strips of the portal and mesenteric veins and the segment C of the inferior vena cava did not respond to clonidine. According to the relative sensitivities to phenylephrine and clonidine, those veins which responded to clonidine could be divided into three groups. (1) The veins in which the sensitivity to phenylephrine was higher than to clonidine: longitudinal strips of the portal vein and segment C of the inferior vena cava, (2) the veins whose sensitivity to phenylephrine was lower than to clonidine: the saphenous, cephalic, femoral and external jugular veins, (3) the vein whose sensitivity to the two agonists was comparable: longitudinal strips of the mesenteric vein. Subtype characteristics were further analyzed in the saphenous vein and in the portal vein using prazosin, phentolamine and yohimbine as antagonists. Analysis of Schild plots to noradrenaline suggested that a mixed population of alpha-adrenoceptor subtypes might be present in the saphenous vein, whereas a rather homogeneous population of a single subtype might occur in the portal vein. The results of the antagonism experiment against phenylephrine and clonidine suggested that contractions of the saphenous vein are mediated by both alpha 1- and alpha 2-adrenoceptors whereas contractions of the portal vein are exerted mainly through alpha 1-adrenoceptors. The results suggest that there may be a distinct regional difference with respect to postsynaptic alpha- adrenoceptor subtypes in the canine venous system.

ABSTRACT-In the course of evolution, two remarkable changes seem to have occurred in vertebrate circulation: the appearance and development of the "endothelium or endothelial tubular system" and "sympathetic nerve /medial smooth muscle system". In the present article, some relevant literature is reviewed and discussed. Absence of endothelium in the vascular wall of most invertebrates had been known and was confirmed by recent electron microscopic studies. The medial smooth muscle is rather proper to vertebrate vessels. It seems to have appeared after emergence of and in association with the endothelial tubular system. Phylogenetically, the parasympathetic nervous system is thought to be older than the sympathetic system. The former is distributed to viscera and the latter developed in close relation with the vascular system. It is assumed that during evolution, a circulatory system composed of the heart and endothelial tubular system first formed in vertebrates, medial smooth muscle then appeared for regulation of the system, and innervation of the muscle tissue took place. This sequence of development assumed for phylogenesis is actually realized in the ontogenetic processes. We thus propose a hypothesis that the "sympathetic nerve /medial smooth muscle system" may be regarded as a new neuroeffector mechanism that developed for systemic regulation of the endothelium-lined closed vascular system in vertebrates. A few implications of the hypothesis are presented.

Contractile responses of isolated dog veins to bradykinin were studied. Responses to norepinephrine were taken as standards. According to their sensitivity to bradykinin, the veins obtained from 14 sites of the venous system were divided into two groups, while all the veins were almost uniform in their sensitivity to norepinephrine. One group has high sensitivity to bradykinin and the other has low sensitivity. The former includes the pulmonary, hepatic, splenic, and portal veins, the anterior vena cava, and the upper and the middle divisions of the posterior vena cava. The latter includes the external jugular, cephalic, azygos, femoral, and saphenous veins, and the lower division of the posterior vena cava. The responses of the renal vein were intermediate. A striking correlation was noted between the distribution of bradykinin sensitivity and the genesis of the venous system. Five bioactive peptides other than bradykinin were also studied. Only angiotensin induced contraction in some preparation, but, as a whole, caerulein, eledoisin-related peptide, oxytocin and vasopressin rarely showed contractile activity.