Hemodynamic response to vasopressin during V1-receptor antagonism in baroreflex-deficient subjects

Abstract

Six quadriplegic subjects and 6 control subjects received high-dose arginine vasopressin (AVP) infusions at rates of 500, 1,000, 2,000, and 4,000 microU.kg-1.min-1 in consecutive 10-min intervals. Six additional quadriplegic subjects received low-dose AVP infusions at rates of 50, 100, 200, 400, and 800 microU.kg-1.min-1. All subjects were studied once with and once without administration of a selective V1-receptor antagonist. During high-dose AVP infusions without V1-receptor blockade, mean arterial pressure (MAP) increased from 80 +/- 4 to 87 +/- 5 mmHg (P < 0.05) in quadriplegic subjects but was unchanged in control subjects. In the presence of V1-receptor blockade, MAP decreased from 75 +/- 4 to 58 +/- 4 mmHg (P < 0.001), and heart rate (HR) increased from 61 +/- 5 to 80 +/- 5 beats/min (P < 0.001) in quadriplegic subjects. In the studies on control subjects, MAP decreased only from 75 +/- 3 to 72 +/- 5 mmHg (P < 0.05), whereas HR increased from 64 +/- 4 to 87 +/- 4 beats/min (P < 0.001). Plasma renin activity (PRA) increased in both quadriplegic and control subjects. The effects of low-dose AVP infusions on MAP, HR, and PRA in quadriplegic subjects were similar to those observed during high-dose infusions. Thus, in the absence of baroreceptor-mediated sympathetic nervous system responses, a vasodilatory effect of AVP that is capable of producing marked reductions in MAP can be demonstrated in the presence of V1-receptor blockade.

Acute Changes in Systemic Hemodynamics and Serum Vasopressin After Complete Cervical Spinal Cord Injury in Piglets

“…After cervical and upper thoracic SCI, unopposed parasympathetic pathways predominate and worsen hemodynamic control systems both acutely and chronically. The biochemical mechanisms involved include an initial increase followed by a prolonged, chronic decrease in circulating catecholamines, impaired vascular responses to vasopressin, and increased nitric oxide-mediated vasodilation [18,[37][38][39][40]. Chronic changes in alpha-adrenergic receptor sensitivity have also been recognized and, along with other mechanisms, may predispose patients to lifethreatening episodes of autonomic dysreflexia [41,42].…”

“…In individuals with chronic SCI, diurnal variation in serum AVP concentration is attenuated and can lead to nocturnal enuresis, which is effectively treated with exogenous vasopressin [46,47]. The vasoconstrictive actions of AVP are well known; however, AVP also has vasodilatory properties at least in part via activation of vasopressin-2 (V 2 ) receptors, as hypotension has been observed in individuals with chronic quadriplegia after administration of a V 1 receptor antagonist [39,40,48,49]. This study is the first to measure acute changes in serum AVP concentration in response to SCI.…”

Discovery of novel selective hypotensive vasopressin peptides that exhibit little or no functional interactions with known oxytocin/vasopressin receptors

“…Nevertheless, it should be recognized that cholinoceptor and α‐adrenoceptor blockade by atropine and phenoxybenzamine might have interrupted the efferent outflow of central sympathetic inhibition and hence reduced the vasodepressor response. AVP is known to affect baroreflex and inhibit central sympathetic outflow, causing a decrease in heart rate and cardiac output (Cowley et al , 1984; Webb et al , 1986; Shimizu et al , 1993; Huch et al , 1995). Thus, a central action for the hypotensive VP peptides could not be ruled out in our experiments.…”

“…Regionally, VP can induce vasodilation (Liard, 1988; Naitoh et al , 1993; Nakanishi et al , 1995; Tagawa et al , 1995; van Lieburg et al , 1995). It also enhances the arterial baroreflex, leading to a depression of heart rate and cardiac output (Cowley et al , 1984; Webb et al , 1986; Shimizu et al , 1993; Huch et al , 1995). It is now generally accepted that VP may play an important role in maintaining systemic blood pressure and in regulating regional blood flows during extreme hemodynamic alterations such as in a hypovolemic state (Schwartz & Reid, 1983; Landry et al , 1997; Reid, 1997).…”

Cardiovascular effects of vasopressin following V1 receptor blockade compared to effects of nitroglycerin

“…However, the mechanisms involved in the vasodilatory response to AVP are incompletely understood and may not be uniformly the same in all segments of the circulation. Although there is evidence that AVP-induced vasodilation may involve V 1 receptors in some highly localized vascular beds (16,17), a vasodilatory effect of AVP has been most clearly demonstrated following V 1 -receptor antagonist administration (13,20,27,28). In early studies reported by Schwartz and Reid (28), V 1 -receptor antagonist administration in water-deprived conscious dogs was shown to produce hemodynamic changes that were the opposite of those usually associated with increased levels of AVP, i.e., cardiac output (CI), heart rate (HR), and plasma renin activity (PRA) were increased.…”