In this study we found that, in 31 normal subjects, close to 90% of circulating arginine vasopressin (AVP), measured by radioimmunoassay, was associated with platelets. By using routine methods of centrifugation, which do not completely separate platelets, the normal range of plasma vasopressin was higher by twofold than the normal range in platelet-free plasma prepared by differential centrifugation, which was 1.4 +/- 1.0 sd pg/ml. Platelet vasopressin was 12.9 +/- 5.7 pg/ml. Patients with congestive heart failure had, on average, an elevated platelet-free plasma AVP, as did two patients with thrombocytopenia and one with thrombocytosis. Patients with essential hypertension had slightly high levels of platelet-free plasma AVP and demonstrated an abnormal inverse relationship between platelet-free plasma AVP and serum osmolality. Immunoreactive platelet vasopressin was slightly low in patients with essential hypertension and was subnormal in patients with congestive heart failure. These studies demonstrate that platelets normally present in centrifuged plasma cause an overestimation of the plasma vasopressin levels. Until the physiological meaning of plasma and platelet-bound AVP is understood, studies of circulating vasopressin should probably assess both plasma and platelet AVP levels.

Plasma and platelet vasopressin in essential hypertension and congestive heart failure.

We determined quantitatively the importance of vasopressin (AVP) release in the regulation of arterial pressure during hemorrhagic hypotension in dogs. The recovery of arterial pressure after rapid hemorrhage was studied in 10 dogs with spinal cord destruction below the level of C-l to remove efferent sympathetic nerve activity. Bilateral nephrectomy was used to remove the reninangiotensin system. Results for this group were compared to those for another group of dogs in which the entire central nervous system, including the pituitary gland, were removed surgically. In all groups, arterial pressure was lowered rapidly from an average control value of 106 ± 2 (mean ± SE) to 51 ± 1 mm Hg by hemorrhage. In dogs with spinal cord destruction and bilateral nephrectomy, arterial pressure rose from 51 mm Hg to 89 ± 3 mm Hg in 3 minutes and stabilized at that level over the next 30 minutes, representing a 71% compensation of arterial pressure. Left atrial pressure fell from 3.3 to 0.8 mm Hg during hemorrhage and subsequently rose only 12% during the hemorrhage. Plasma AVP rose during hemorrhage from 19 ± 2 to 75 ± 10 μU/ml. Injection of the competitive AVP inhibitors, [1-deaminopenicillamine, 4-valine]-8-D-arginine-vasopressin (dPVDAVP), completely reversed the effects and returned the compensated pressure to 50 mm Hg. In the complete absence of the central nervous system, arterial pressure compensation averaged only 10 ± 3%. Plasma osmolality, sodium and potassium concentrations, hematocrit, and heart rate were unchanged in all experimental groups. The relationships involved in the AVP-arterial pressure control system were determined quantitatively and analyzed. A systems analysis using experimentally determined values for AVP secretion and metabolism, plasma AVP, and changes in arterial pressure closely predicted the changes observed during hemorrhage. It appears from this study that AVP has potent systemic vasoconstrictor actions enabling it to make a significant contribution in the restoration of arterial pressure during hemorrhage. Circ Res 46: 58-67, 1980

Evidence and quantification of the vasopressin arterial pressure control system in the dog.

To further characterize the role of vasopressin in DOC-salt hypertension, four groups of unilaterally nephrectomized rats were studied: control rats given no further treatment, rats treated with DOC and given 1% saline to drink, or rats treated with only DIC or 1% saline had similar pressor responses to exogenous vasopressin and angiotensin II. Within the DOC-salt group, two populations of rats were identified: one with normal pressor responsiveness to vasopressin, and one with markedly enhanced pressor responsiveness to vasopressin. Incidence of enhanced responsiveness increased with duration of treatment. Urinary excretion of vasopressin was elevated in the 1% saline and DOC-salt groups after 1 week of treatment, and in the DOC group after 4 weeks. However, the plasma vasopressin concentration was elevated only in the rats treated with both DOC and saline. It is suggested that vasopressin is essential for the expansion of blood volume in the early stages of DOC-salt hypertension, and functions as a direct pressor agent only in the later stages.

Pressor responsiveness to vasopressin in the rat with DOC-salt hypertension

Although the cardiovascular actions of vasopressin (VP) have been examined systematically only in recent years, Oliver and Schafer (1895) first observed the vaso-pressor activity of pituitary gland extracts in 1895. This was soon confirmed by three other investigators (Howell, 1898; Livon, 1898; von Cyon, 1898) and Howell demonstrated that the pressor principle resided in extracts of the posterior lobe. It was from these early observations that VP derived its name. The antidi-uretic actions of VP were not observed until 1913, when two physicians working independently, Farini (1913), in Italy, and Von den Velden (1913), in Germany, reported successful treatment of patients with diabetes insipidus by injections of posterior pituitary extracts. With the 1924 demonstration of the antidiuretic effects of posterior pituitary extracts on the isolated kidney by Starling and Verney (1924), the antiduretic role of the neurohypophysis became the predominant aspect of interest related to VP. It became clear that this hormone was of vital importance for the conservation of body fluids and that, although pressor activity was widely observed, it was evident that these actions required amounts far in excess of those required for maximal antidiuretic activity (Saameli, 1968; Sawyer, 1971; Nakano, 1974). These important antidiuretic actions of VP are reviewed in Chapter 9.

Cardiovascular Actions of Vasopressin

To determine the influence of vasopressin on baroreceptor reflex mechanisms, baroreflex function in Brattleboro rats was compared with that in normal Long-Evans rats. Baroreflex function was assessed in conscious unrestrained rats during increases in blood pressure with phenylephrine (200 Mg/kg per min for 10 seconds). The baroreflex function line was obtained by plotting the log (pulse period) against the preceding systolic pressure on a beat-by-beat basis. The slope of the baroreflex function line (baroreflex function slope) in Long-Evans rats [(19.0 ± 1.4) X 10", mean ± SEM, n = 34] was significantly steeper than that in Brattleboro rats [(6.9 ± 0.6) X 10~\ n = 44, P < 0.001]. A subpressor intravenous infusion of arginine-vasopressin (2 ng/kg per min for 2 hours), which elevated plasma vasopressin to 48.1 ± 6.8 pg/ml, caused bradycardia and increased the baroreflex function slope in Brattleboro rats, from (7.5 ± 1.0) x 10"" to within the normal Long-Evans range [(17.0 ± 0.8) x 10~\ n = 7, P < 0.001]. The basal pulse period and the baroreflex function slope in Brattleboro rats [(7.0 ± 0.9) x 10~] was also increased significantly to (12.0 ± 1.7) X 10"* (n = 11, P < 0.01) by an infusion of l-desamino-8D-arginine vasopressin, (2 ng/kg per min for 2 hours), a vasopressin analogue with potent antidiuretic but minimal vascular actions. Acute volume expansion, which increased body weight significantly, did not change the baroreflex function slope in Brattleboro rats [(7.7 ± 1.1) X 10" vs. (8.2 ± 1.7) X 10~\ n = 6]. A specific vasopressin vascular receptor antagonist [d(CH2)5 Tyr(Me)AVP], although blocking the pressor effect of exogenous vasopressin, did not change the pulse period or the baroreflex function slope [(16.0 ± 2.3) X 10~* vs. (19.0 ± 1.7) X 10"*, n = 6)] in normal Long-Evans rats. The results obtained in Brattleboro rats and the change in baroreflex sensitivity brought about by infusions of vasopressin and DDAVP provide strong evidence that vasopressin may be an important physiological modulator of baroreflex function. (Circ Res 53: 140-149, 1983)

Restoration of suppressed baroreflex sensitivity in rats with hereditary diabetes insipidus (Brattleboro rats) by arginine-vasopressin and DDAVP.

The role of vasopressin in blood pressure control and in the pathogenesis of one-kidney Goldblatt hypertension was investigated in the conscious dog. Intravenous infusion of synthetic arginine vaso...

Plasma vasopressin in blood pressure homeostasis and in experimental renal hypertension.

1. The role of vasopressin in blood pressure control and in the pathogenesis of one-kidney Goldblatt hypertension in the conscious dog was investigated. 2. Infusion of synthetic arginine vasopressin to elevate plasma levels approximately five-fold caused bradycardia in normal dogs and increase in mean arterial blood pressure in dogs with pharmacological autonomic blockade. 3. A similar degree of elevation of plasma vasopressin concentration was observed after mild non-hypotensive haemorrhage. 4. Renal artery constriction in unilaterally-nephrectomized dogs caused a rise in plasma renin activity and only a doubling of plasma vasopressin concentration, but a marked rise in mean arterial blood pressure. 5. Vasopressin may play a role in normal cardiovascular homeostatic responses, but its role in the pathogenesis of this form of hypertension is unlikely to be significant.

P. T. Pullan

Papers

Plasma vasopressin in blood pressure homeostasis and in experimental renal hypertension.

The Role of Vasopressin in Blood Pressure Control and in Experimental Hypertension