Burton M. Altura

Magnesium and contraction of arterial smooth muscle.

Abstract The present in vitro experiments demonstrate that reduction in [Mg2+]0 induces contractile responses in rat aortic strips; the greater the reduction in [Mg2+]0, the greater the magnitude of the mechanical response. These contractile responses are dependent upon the [Ca2+]0 and the polarity of the vascular smooth muscle cell membrane. Adrenergic, cholinergic, serotonergic, or histaminergic antagonists do not interfere with these Mg2+-dependent contractile responses. Increases in [Mg2+]0 above 1.2 mM (e.g., 2.4 and 6.0 mM), on the other hand, inhibits spontaneous contractile activity and lowers basal tension; these latter findings are not due to hyperosmolarity. Exposure of rat aorta to Mg2+-free Krebs-Ringer for 1 hr differentially affects the contractile responses induced by catecholamines, serotonin, angiotensin, barium, and neurophypophyseal hormones. In addition, Mg2+-free solution results in a lowering of the threshold and maximal force development of Ca2+-induced contractions of depolarized rat aorta. These data support the suggestions that (1) certain divalent cation sites in vascular smooth muscle may be nonspecific in regard to Mg and Ca, and (2) Mg ions may be important in regulating permeability, translocation and/or binding of Ca ions in vascular muscle.

Sex as a factor influencing the responsiveness of arterioles to catecholamines.

Abstract The present in vivo experiments on rat mesenteric arterioles, using a high magnification (up to 4000 ×) image-splitting television microscope recording system, demonstrate that dose—response curves for the constrictor catecholamines epinephrine and norepinephrine in female rats are significantly shifted in a parallel manner to the left of those obtained in male rats. The maximal arteriolar contractile (i.e., lumen diameter narrowings) responses to the catecholamines were, however, not altered by the sex differences. Dose—response curves for constrictions induced by dopamine or phenylephrine were not affected by a difference in sex. The sex-linked differences, observed in the present study, thus appear to be specific for catecholamine molecules exhibiting not only a catechol nucleus but an hydroxyl group on the β-carbon of the side chain. These findings could be interpreted as support for a role of sex hormones in control of blood flow.

Heterogeneity of drug receptors in different segments of rabbit thoracic aorta

Abstract The present experiments demonstrate that heterogeneity of drug receptors, which subserve contraction, exist within different segments of a single arterial blood vessel. There appears to be an absolute, progressive loss in most drug receptors (or reactive smooth muscle cells) proceeding down the rabbit thoracic aorta from the aortic arch to diaphragm. The loss of contractile response to certain vasoactive drug stimuli parallels the loss in reactivity to catecholamines; in other cases there is no parellelism to catecholamine reactivity. Statistical analysis of the data presented suggests that the magnitudes of some drug-induced contractile responses appear to be dependent on the absolute mass of smooth muscle cells rather than the numbers of receptors per cell. In addition, a progressive segmental increase in calcium content was found proceeding down the rabbit thoracic aorta.

Selective microvascular constrictor actions of some neurohypophyseal peptides

Abstract The present experiments, using an image-splitting television microscope recording system, show for the first time that it is possible to obtain quantitative, complete dose—response relationships for the constrictor actions of a series of vasopressin and oxytocin hormone analogues on all major types of microscopic blood vessels, in situ, in the terminal vascular bed. The findings demonstrate that: (1) the structure—action relationships for neurohypophyseal peptide-induced contractions on microscopic blood vessels may vary with the particular type of muscular microvessel (i.e., arteriole, venule, metarteriole, precapillary sphincter); (2) although basicity in position 8 of the vasopressin hormones is probably important for hormone-receptor affinity on all mammalian somatic blood vessels, including those in the microcirculation, it is not important for intrinsic (contractile) activity; and (3) certain synthetic analogues of the neurohypophyseal peptide hormones exert selective microvascular constrictor actions . Thus, the present data show that some previously synthesized neurohypophyseal analogues exhibit relatively high hormone-receptor affinities (H-RA) for particular types of microvessels while exhibiting very low H-RA for other types of microscopic blood vessels. It is suggested that a heterogeneity of the vasopressin receptor, in mammalian vascular smooth muscle cells, of different types of blood vessels may exist.

Reticuloendothelial Function in Experimental Injury and Tolerance to Shock

Although the morphology, ultrastructure and functions of the reticuloendothelial system (RES) are becoming well documented (64, 72), most of the information is immunologically oriented. The role of the RES in host defense mechanisms in injuries and systemic forms of stress is less understood.

Sequential Changes in Reticuloendothelial System Function After Acute Hemorrhage

Summary Experiments were designed with rats to determine: (i) whether reticuloendothelial system (RES) phagocytic function undergoes quantitative, sequential changes after acute blood loss; and (ii) whether RES phagocytic indices (K values) are correlated with survival or death of the animals. The results indicate that: (i) RES phagocytic function does, indeed, undergo sequential, quantitative changes in animals subjected to various degrees of acute hemorrhagic shock. (ii) The greater the degree of hemorrhagic shock (as determined by mortality), the greater is the magnitude of early RES phagocytic depression. (iii) Animals which survive after various degrees of hemorrhagic shock not only show, with time, progressively improved RES phagocytic indices but exhibit hyperfunctional reticuloendothelial systems. (iv) Animals which succumb from these procedures fail to exhibit either progressively improved K values or hyperfunctional RE systems and thus continue to manifest RE systems which are markedly depressed up until death. Overall, these data could be used to suggest that numerical RES phagocytic indices may be diagnostic and prognostic parameters of the shock syndrome.

Pharmacology of neurohypophyseal hormones and their synthetic analogues in the terminal vascular bed. Structure-activity relationships.

* Presented at the fourteenth annual conference of the Microcirculatory Society, Atlantic City, April 10-11, 1966. From the Department of Anesthesiology, New York University Schools of Medicine, New York, New York and the Departments of Anesthesiology and Physiology, Albert Einstein College of Medicine, Bronx, New York 10461. This investigation was supported, in part, by research grants from the USPHS (HE-09042 and HE-11391). † Present address: Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, New York 1046

Glucocorticoid-Induced Protection in Circulatory Shock: Role of Reticuloendothelial System Function

Summary Experiments with rats indicate that: (i) hydrocortisone sodium succinate (HC) and methylprednisolone sodium succine (MP) enhance survival after hemorrhage; (ii) MP is approximately 10-times more potent than HC; (iii) both HC and MP are more efficacious if administered prior to hemorrhage; (iv) efficacy of post-shock therapy with both steroids is not only time- but dose-dependent; and (v) HC and MP can ameliorate or completely prevent the early RES phagocytic depression observed in circulatory shock. Overall, these data could be used to suggest that: (i) the RES may play a pivotal role in the beneficial actions of synthetic adrenocorticosteroids in circulatory shock, and (ii) numerical RES phagocytic indices may be diagnostic and prognostic parameters in circulatory shock therapy. The author wishes to express his thanks to Mrs. J. Hanley and Mr. R. W. Burton for their technical assistance. We are grateful to Marvin Berkowitz of the UpJohn Company for generously providing us with the Solu-Cortef and Solu-Medrol used in these studies.

Microcirculatory Actions of Polypeptides and Their Use in the Treatment of Experimental Shock

In the normal regulation of the microcirculation it is generally accepted that the catecholamines serve as the undifferential tonic constrictor influence on the muscular microvessels(1). To achieve appropriate local vasomotor behavior, which must be adjusted from moment to moment, the unselective constrictor influence of the catecholamines is thought to be modulated by a host of local tissue mediators such as serotonin, histamine, acetylcholine, glucocorticoids, and metabolic by-products as well as by the ratio of alpha to beta adrenergic receptors in different vessel s (1–5). These local tissue mediators probably also include low molecular weight polypeptides. Until recently, most interest in these tissue vasoactive polypeptides has focused on the kinin class of compounds which are thought to essentially dilate vessels and/or depress vasomotor activity(6). But there is little question that these locally acting substances also include polypeptides which are essentially excitor such as angiotensin and the neurohypophyseal polypeptide hormones (NHPH). Ever since the classic work of August Krogh and Sir Henry Dale with pituitrine, it has been repeatedly suggested by many workers that the posterior pituitary hormones lend fine adjustment to the tonic constrictor action of the catecholamines (see ref.7 for citations).

Calcium Content and Force of Drug-Induced Contractions of Arterial Muscle During Recovery in vitro

Summary and Conclusions Studies were designed, using rabbit aortic strips, to investigate the possible role calcium (Ca2+) ions play in the recovery of depressed, drug-induced contractions of excised, isolated blood vessels. The present experiments demonstrated that: (i) excision of aorta from intact rabbits and the subsequent surgical preparation and incubation of helical strips, at physiologic temperature in vitro, severely impairs the development of full sensitivity, of these aortic smooth muscle cells, to a variety of vasoactive substances for a period of 3 hr. (ii) A close relationship was found to exist between the ability or inability of different vasoactive drugs (e.g., epinephrine, histamine, potassium, and barium) to induce a maximal contractile response and the total Ca2+ content (as quantitatively determined by atomic absorption spectrophotometry). And (iii) mechanical (surgical) injury may alter the in vivo Ca2+ content of arterial smooth muscle.