Volume 21 of the series Advances in Experimental Medicine and Biology pp 187-196

Structure-Activity Relationships of Neurohypophyseal Polypeptides on Different Types of Isolated Mammalian Blood Vessels

  • Burton M. AlturaAffiliated withDepartments of Anesthesiology and Physiology, Albert Einstein College of Medicine

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Up until the isolation and synthesis of vasopressin in 1953 by du Vigneaud vasopressin was given little serious thought as a useful vasoactive drug because of its well documented coronary constrictor action. Interestingly, however, there is now good evidence to indicate that at least two synthetic neurohypophyseal hormone (NHPH) analogues, namely 2-phenylalanine-8-lysine vasopressin (PLV-2) and 8-ornithine vasopressin, may have significant antiarrhythmic properties in man (see references in 9). Additional experimental studies indicate that at least one of these NHPH analogues, namely PLV-2 (the only one so far investigated in animal coronary circulation), increases the relative myocardial blood flow in rats (16) and relaxes a variety of isolated bovine coronary arteries (1). Furthermore, it has been demonstrated that when PLV-2 was used as a local vasoconstrictor in skin flaps it did not produce any decrease in tissue oxygen tensions, while epinephrine did (20). Possibly more importantly, our laboratory found that PLV-2 improved survival in animals subjected to various forms of shock (9, 10, 11, 13, 19) and suggested this might be due to its unusual microcirculatory effects as observed by direct in-vivo microscopy (4, 7–12, 19). In view of such findings we initiated systematic pharmacologic and structure-activity studies of the NHPH, and particularly their synthetic analogues, not only at the microcirculatory level but on various types of isolated mammalian blood vessels since the latter would be divorced from any in-vivo effects of metabolism and blood flow.