vasopressin--1-(1-mercaptocyclohexaneacetic-acid)-2-(o--methyl-l-tyrosine)-8-l-arginine- and Aortic-Coarctation

We investigated the genesis of the hypertensive response to acute (45 min) aortic constriction in two models of chronic vasopressin (AVP) deficiency, i.e., Brattleboro strain and median eminence lesioned (MEL) Wistar rats. The same degree of partial aortic constriction, with a pneumatic cuff placed around the abdominal aorta, yielded a sudden and maintained increase in carotid pressure to the same extent in Brattleboro, MEL and sham-MEL rats. Blockage of AVP V1 receptors with d(CH2)5Tyr[Me]AVP did not affect the hypertensive response of Brattleboro or MEL rats, but gradually blunted the response of sham-MEL rats. Blockage of angiotensin II receptors with saralasin blunted the hypertensive response of the AVP-deficient subjects throughout the experiment, but only delayed (5-15 min) the onset of hypertension in sham-MEL rats. Simultaneous blockage of AVP and angiotensin II blunted the hypertensive response of sham-MEL and AVP-deficient rats throughout the experiment. These data demonstrate that when one vasoactive system is chronically absent, as is the case for AVP in Brattleboro and MEL rats, the renin-angiotensin system plays the major role in the pathophysiology of acute aortic coarctation hypertension.

Topics: Angiotensin Receptor Antagonists; Animals; Antidiuretic Hormone Receptor Antagonists; Aortic Coarctation; Arginine Vasopressin; Blood Pressure; Chronic Disease; Female; Hormone Antagonists; Hypertension; Male; Median Eminence; Rats; Rats, Brattleboro; Rats, Wistar; Renin-Angiotensin System; Saralasin

The present study was designed to investigate the effect of a lack of vasopressin resulting from electrolytic lesion of the median eminence of the hypothalamus on the acute 45-min aortic coarctation hypertension elicited in conscious rats by means of a pneumatic cuff placed around the aorta above the renal arteries. Forty-eight hours after lesion, aortic constriction elicited a prompt (5-min) rise in mean carotid pressure from 115 +/- 2 to 149 +/- 2 mmHg, followed by a gradual decline to 129 +/- 2 mmHg. In contrast, sham-lesioned rats exhibited a prompt hypertensive response from 118 +/- 2 to 157 +/- 2 mmHg that leveled off throughout the experiment. Lesioned rats treated with saralasin presented a blunted hypertensive response (within 125 +/- 2 to 130 +/- 2 mmHg), whereas sham-lesioned rats showed only a delay in the onset of hypertension. The hypertensive response of lesioned rats was unaffected by the vasopressin antagonist [d(CH2)5Tyr(Me)]AVP, whereas sham-lesioned rats submitted to this treatment presented a prompt rise in pressure followed by a gradual decline at the end of the experiment. Lesioned and sham-lesioned rats treated with saralasin plus vasopressin antagonist showed a blunted hypertensive response throughout the experiment. These data demonstrate that the integrity of the median eminence plays a pivotal role in the maintenance (30-45 min) of acute aortic coarctation hypertension, presumably involving the release of vasopressin from the neurohypophysis, whereas angiotensin II mainly accounts for the prompt (5-15 min) rise in pressure.

Topics: Acute Disease; Animals; Aortic Coarctation; Arginine Vasopressin; Blood Pressure; Hypertension; Male; Median Eminence; Rats; Rats, Wistar; Saralasin; Vasopressins

The hemodynamic responses and the role of renal nerves in the physiopathogenesis of acute (45 min) aortic coarctation hypertension were studied in conscious rats. The hemodynamic responses elicited by aortic constriction in intact and bilaterally nephrectomized rats were analyzed by means of miniaturized pulsed-Doppler flow probes. Anephric rats presented a smaller increase in mean carotid pressure (MCP) and calculated aortic resistance during aortic coarctation than did intact animals. Reflex bradycardia throughout the experiment did not differ significantly between the two groups. The pressor response following aortic coarctation in untreated renal-denervated rats was similar to that found in intact subjects. Renal-denervated rats previously treated with V1-vascular arginine vasopressin antagonist [d(CH2)5Tyr(Me)AVP] showed the same hypertensive response as control renal-denervated rats. Previous treatment of renal-denervated rats with saralasin (an angiotensin II antagonist) produced a significant reduction in the hypertensive response throughout the experiment when compared to untreated renal-denervated rats. Similarly, rats treated with the vasopressin antagonist plus saralasin showed a blunted hypertensive response following aortic coarctation. The results for rats previously treated with vasopressin antagonist plus saralasin did not differ from those obtained with saralasin alone. Overall, the results of aortic coarctation hypertension obtained in the present study indicate that: 1) Anephric rats showed a blunted hypertensive response due to the lack of neuro-humoral release of vasopressor substances (e.g. angiotensin II and vasopressin) triggered by the kidneys, when only the mechanical factor of constriction was present; 2) The lack of afferent feedback from the kidneys in renal-denervated rats for vasopressin release from the central nervous system allowed angiotensin II to play the major physiopathological role associated with the mechanical factor in the hypertensive response.

Topics: Animals; Aorta, Abdominal; Aortic Coarctation; Arginine Vasopressin; Denervation; Hemodynamics; Hypertension; Kidney; Male; Nephrectomy; Neurons, Afferent; Rats; Rats, Inbred Strains; Saralasin

The role of vasopressin (AVP) and angiotensin II (ANG II) in the onset of acute (45 min) aortic coarctation hypertension was studied in conscious rats. Changes in mean carotid pressure (MCP) and heart rate (HR) were measured in four groups of rats. Control rats presented a hypertensive response that attained a plateau 5 min after coarctation and remained near this level throughout the experiment. Rats treated with AVP V1-vascular receptor antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-(O-methyl)tyrosine]arginine vasopressin [d(CH2)5Tyr(Me)AVP] presented a prompt rise in MCP similar to the control rats, but in contrast to this group, the MCP started to decline progressively. Rats treated with saralasin presented a delay in the onset of hypertension right after coarctation but slowly attained values similar to those for control rats. In contrast, the rats treated with AVP antagonist plus saralasin showed a blunted MCP elevation throughout the experiment. Reflex bradycardia observed in the rats treated with saralasin or the AVP antagonist plus saralasin was similar to that observed in the control rats, whereas for the group treated only with AVP antagonist, the reflex bradycardia was more intense than for the other three groups, indicating an increased sensitivity of the baroreflex. These data demonstrate that in addition to the mechanical effect of aortic constriction, both ANG II and AVP participate in the onset of acute aortic coarctation hypertension. Moreover, the results indicate that ANG II acts on the prompt (5 min) rise in pressure, whereas AVP is responsible for the maintenance (30-45 min) of the arterial pressure elevation.

Topics: Acute Disease; Angiotensin II; Animals; Aortic Coarctation; Arginine Vasopressin; Blood Pressure; Carotid Arteries; Heart Rate; Hypertension; Male; Rats; Rats, Inbred Strains; Saralasin; Vasopressins