pituitrin and Hypertension--Malignant

The vasoconstrictor and vasopressor actions of vasopressin have been revealed in recent research through the use of highly specific and sensitive radioimmunoassays, employment of peptide antagonists, and comparison with an animal model which has hereditary absence of this hormone, the Brattleboro rat. Factors now known to modify the pressor effect of vasopressin are the baroreflexes, local vascular prostaglandin production, and a specific interaction with angiotensin II. In experimental models the volume retaining, but not the vasoconstrictor effect of vasopressin is necessary for mineralocorticoid-salt hypertension. Vasopressin contributes directly to the increase in arterial pressure of glycerol induced acute renal failure. In nephrectomized rats, plasma vasopressin is elevated and contributes directly to maintenance of pressure. Vasopressin antagonism may reduce arterial pressure in Goldblatt 1 and 2 kidney hypertension and in one genetic model, spontaneously hypertensive rat (SHR), but the peptide is not necessary for hypertension in these models. Plasma vasopressin is reduced in primary aldosteronism, but may be elevated in malignant hypertension. In essential hypertension, there is considerable disagreement among various studies in which plasma vasopressin, urine vasopressin excretion, platelet associated vasopressin, or vasopressin-neurophysin were measured as to whether there is evidence for increased secretion of vasopressin. Only preliminary studies of vasopressin antagonism in clinical hypertension have been reported. At present, there is no conclusive evidence that elevated vasopressin secretion occurs or is necessary for any form of clinical hypertension.

Topics: Acute Disease; Acute Kidney Injury; Animals; Central Nervous System Diseases; Desoxycorticosterone; Humans; Hypertension; Hypertension, Malignant; Hypertension, Renal; Hypertension, Renovascular; Kidney Failure, Chronic; Rats; Rats, Brattleboro; Rats, Inbred SHR; Vasopressins

Topics: Adrenergic beta-Antagonists; Anemia, Hemolytic; Animals; Antihypertensive Agents; Cyclic AMP; Factor XII; Humans; Hydralazine; Hypertension, Malignant; Labetalol; Platelet Aggregation; Prostaglandins F; Rabbits; Rats; Renin-Angiotensin System; Thromboplastin; Vasopressins; Water-Electrolyte Imbalance

Topics: Angiotensin II; Animals; Blood Pressure; Hypertension, Malignant; Hypertension, Renal; Hyponatremia; Juxtaglomerular Apparatus; Osmolar Concentration; Pepstatins; Plasma Volume; Rats; Renin; Saralasin; Vasopressins; Water-Electrolyte Imbalance

Plasmapheresis (PP) was used in 28 patients with medication-resistant high arterial hypertension (AH). PP-induced changes in plasma renin activity and blood aldosterone, angiotensin II and antidiuretic hormone levels of patients with high AH are shown to be a compensatory-adaptive response, maintaining homeostasis. PP sessions (27 ml/kg body weight at a rate of 0.22 ml/kg/min, at the maximum) do not produce renin-angiotensin-aldosterone activation. Long-term hypotensive effect of PP in cases of high AH might be related to a gradual decrease in blood angiotensin II and systemic aldosterone synthesis. It is suggested that the hypotensive effect of PP may be due to an intricate interaction of effects, with humoral, receptor and circulatory re-adjustments of arterial BP control being the most prominent among those.

Topics: Adult; Chronic Disease; Drug Resistance; Female; Humans; Hypertension; Hypertension, Malignant; Male; Middle Aged; Plasmapheresis; Renin-Angiotensin System; Time Factors; Vasopressins

The role of vasopressin (VP) in maintaining blood pressure in malignant two-kidney one-clip Goldblatt hypertension in chronically catheterized conscious rats was investigated by studying the effect of two structurally different VP pressor antagonists. Injections of either 20 micrograms/kg of dPTyr(Me)AVP or 10 micrograms/kg of d(CH2)5Tyr(Me)AVP failed to alter mean arterial pressure or heart rate, although both antagonists completely inhibited the pressor response elicited by exogenous VP. These results suggest, that VP is not involved as a pressor hormone in the maintenance of high blood pressure in this type of experimental hypertension.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Female; Hypertension, Malignant; Hypertension, Renovascular; Rats; Vasopressins

To investigate the possible role of vasopressin (VP) in the maintenance of DOC-salt hypertension the effect of two VP pressor antagonists on mean arterial pressure and the pressor responsiveness to exogenous VP were studied in conscious, freely moving rats with malignant DOC-salt hypertension. Intravenous injections of either 20 micrograms/kg of dP Tyr(Me)AVP or 10 micrograms/kg of d(CH2)5Tyr(Me)AVP had no significant effect on mean arterial pressure and heart rate, although both antagonists almost completely abolished the pressor response to VP. Furthermore, the animals with DOC-salt hypertension exhibited decreased pressor responsiveness to exogenous VP. The present findings strongly suggest that VP is not essential as a pressor hormone for maintaining blood pressure in malignant DOC-salt hypertension.

Topics: Animals; Arginine Vasopressin; Desoxycorticosterone; Dose-Response Relationship, Drug; Female; Hypertension, Malignant; Rats; Sodium Chloride; Vasopressins

We studied 29 patients with malignant hypertension and 28 patients with the syndrome of inappropriate antidiuretic hormone secretion to assess the relation of plasma vasopressin to blood pressure in states of acute and chronic vasopressin excess. In the patients with malignant hypertension, vasopressin levels were elevated (13 +/- 2 pg per milliliter. [+/- S.E.M.]) but did not correlate with arterial pressure; however, in normal volunteers, blood pressure did not rise when vasopressin was increased beyond these levels through infusion of the peptide. In the patients with inappropriate antidiuretic hormone secretion, blood pressure was not elevated, but vasopressin was raised (39 +/- 7 pg per milliliter) and did not correlate with systolic or diastolic pressure. These data do not support the concept that an acute or chronic excess of vasopressin makes an important contribution to the regulation of blood pressure.

Topics: Adult; Blood Pressure; Female; Humans; Hypertension, Malignant; Inappropriate ADH Syndrome; Male; Middle Aged; Vasopressins

Topics: Adult; Female; Hemodynamics; Humans; Hypertension; Hypertension, Malignant; Male; Vasopressins

Topics: Contraceptives, Oral; Female; Humans; Hypersensitivity, Delayed; Hypertension, Malignant; Male; Renin-Angiotensin System; Smoking; Vasopressins

Topics: Animals; Desoxycorticosterone; Electrolytes; Hypertension; Hypertension, Malignant; Male; Plasma Volume; Rats; Sodium Chloride; Vasoconstrictor Agents; Vasopressins; Water

Topics: Animals; Antigen-Antibody Reactions; Blood Pressure; Body Weight; Hematocrit; Hypertension; Hypertension, Malignant; Rats; Vasopressins; Water-Electrolyte Balance

Male Sprague-Dawley rats with unilateral renal artery stenosis and a contralateral untouched kidney develop a malignant hypertension (MH) which is characterized by high blood pressures, sodium and water depletion, and subsequent activation of the renin-angiotensin system. In the present studies we found plasma arginine vasopressin (AVP) concentrations-3-fold higher than those in rats with benign renal hypertension, and 4- to 5-fold higher than those in normotensive control rats. Analysis of individual values showed considerable scatter; about 50% of the values fell in the range of benign hypertensive or control rats. When a specific AVP antiserum was injected, iv, into eight conscious unrestrained MH rats, BP transiently fell toward control values in four; in one, BP fell by only 10 mm Hg, and three other MH rats showed no response. In the same rats, injection of a specific angiotensin II antiserum always induced a transient fall in BP. On the basis of these and previously reported observations, we conclude that, subsequent to sodium and water loss and activation of the renin-angiotensin system, vasopressin release is stimulated in a significant number of MH rats and that, in these rats, vasopressin may cause significant systemic vasoconstriction. Thereby vasopressin may contribute to the development of malignant renal hypertension in rats.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Hypertension, Malignant; Hypertension, Renal; Immune Sera; Male; Natriuresis; Rats; Renal Artery Obstruction; Sodium; Vasoconstriction; Vasopressins; Water-Electrolyte Balance

During the onset of malignant hypertension (MH) in rats treated with deoxycorticosterone trimethylacetate (DOC), plasma arginine vasopressin (AVP) concentrations increase tenfold as a consequence of hypovolemia and hyperosmolality. In benign hypertensive (BH) rats, plasma AVP is increased threefold in comparison with control animals. Plasma renin is markedly suppressed in both BH and MH animals. In MH rats, biologically active AVP antiserum lowers blood pressure (BP) transiently to normal or subnormal levels; in BH rats, a small BP-lowering effect of the AVP antiserum is seen. (Biologically active angiotensin II antiserum does not lower BP in MH rats.) The relationship between the height of BP and plasma AVP concentration in DOC hypertensive rats indicates, when compared with that relationship in diabetes insipidus rats infused with AVP, a marked enhancement of the vasopressor effect of AVP. These findings and the earlier observation of vasopressin-induced vascular damage by Byrom (F. B. Byrom, The Hypertensive Vascular Crisis. London: Heinemann, 1969) strongly suggest that ADH is involved as a vasopressor hormone in the pathogenesis of malignant DOC hypertension.

Topics: Angiotensin II; Animals; Antibodies; Arginine Vasopressin; Blood Pressure; Body Weight; Desoxycorticosterone; Diabetes Insipidus; Hypertension; Hypertension, Malignant; Immune Sera; Male; Nephrectomy; Osmolar Concentration; Rats; Renin; Sodium; Urea; Vasomotor System; Vasopressins

Topics: Angiotensin II; Animals; Arteries; Blood Pressure; Capillary Permeability; Humans; Hypertension, Malignant; Necrosis; Renin; Vascular Diseases; Vasopressins

Topics: Adenoma; Adrenal Cortex Neoplasms; Animals; Humans; Hypertension; Hypertension, Malignant; Rats; Vasopressins

Rats with unilateral nephrectomy were offered 1% sodium chloride as drinking fluid and were injected with desoxycorticosterone trimethylacetate (D.O.C.-T.M.A.) at weekly intervals. During the fourth to seventh week after the start of the experiment, malignant hypertension developed in most of the animals: body weight fell, reflecting volume depletion; serum osmolality and serum sodium and urea concentrations increased; in the kidneys malignant nephrosclerosis occurred. In such animals, plasma concentrations of arginine-vasopressin were increased ten-fold in comparison with control animals; intravenous injection of a specific vasopressin antibody resulted in a transient fall of blood-pressure (B.P.) to normal or subnormal levels, while the injection of an angiotensin-I or angiotensin-II antibody did not affect B.P. In control animals none of the antibodies had an effect on B.P. It is concluded that in the pathogenesis of malignant D.O.C. hypertension vasopressin plays a role similar to that of renin-angiotensin in malignant renal hypertension.

Topics: Angiotensin II; Animals; Antibodies; Arginine Vasopressin; Blood Pressure; Body Weight; Desoxycorticosterone; Eating; Hypertension, Malignant; Male; Osmolar Concentration; Rats; Rats, Inbred Strains; Sodium; Urea; Vasopressins

Plasma concentrations of arginine-vasopressin (antidiuretic hormone) have been measured in 40 patients with benign essential hypertension and 12 patients with malignant-phase hypertension. Values tended to be low in the benign phase and high in the malignant phase. 5 normal subjects were infused with synthetic arginine-vasopressin, producing plasma concentrations up to five times the highest value recorded in malignant-phase hypertension, without any effect on blood-pressure. There is no evidence that vasopressin has a direct role in the pathogenesis of benign essential hypertension or its transition to the malignant phase. On the contrary, abnormal vasopressin concentrations may be caused by hypertension.

Topics: Adult; Aged; Arginine Vasopressin; Blood Pressure; Female; Humans; Hypertension; Hypertension, Malignant; Infusions, Parenteral; Male; Middle Aged; Vasopressins

1. The role of arginine-vasopressin in the pathogenesis of malignant deoxycorticosterone (DOC) hypertension of rats was investigated. 2. In rats with malignant DOC hypertension plasma arginine-vasopressin concentrations increased more than tenfold subsequent to volume depletion and a rise of serum osmolality. 3. The injection of a specific antibody serum for arginine-vasopressin caused a marked fall of blood pressure in rats with malignant DOC hypertension, whereas the injection of angiotensin II antiserum did not affect blood pressure. 4. In rats exhibiting a benign course of DOC hypertension plasma concentrations of arginine-vasopressin were increased threefold in comparison with normotensive control rats; the injection of an arginine-vasopressin antiserum induced a significant but small fall of blood pressure. 5. It is concluded that in the pathogenesis of malignant DOC hypertension arginine-vasopressin might play the role that the renin-angiotensin system plays in the pathogenesis of malignant renal hypertension.

Topics: Animals; Arginine Vasopressin; Desoxycorticosterone; Hypertension, Malignant; Male; Osmolar Concentration; Rats; Vasopressins

Topics: Angiotensin II; Diabetes Insipidus; Diet, Sodium-Restricted; Glomerular Filtration Rate; Humans; Hypertension, Malignant; In Vitro Techniques; Kidney Diseases; Male; Middle Aged; Natriuresis; Periodicity; Polyuria; Renin; Vasopressins