The objectives were to determine if ANG II-induced hypertension is maintained by activation of endothelin type A (ET(A)) receptors by endogenous ET-1 and if this effect is influenced by salt intake. Male rats were maintained on high sodium intake (HS; 6 meq/day) or on normal sodium intake (NS; 2 meq/day). Hypertension was produced by intravenous infusion of ANG II (5 ng/min) for 15 days. Five-day oral dosing with the selective ET(A)-receptor antagonist ABT-627 (~2 mg. kg(-1). day(-1)) reduced mean arterial pressure (MAP) to baseline levels in rats on HS receiving ANG II infusion, but it did not affect MAP in normotensive HS controls. In rats on NS, ABT-627 only transiently decreased MAP in rats receiving ANG II and slightly reduced MAP in normotensive controls. ABT-627 produced mild retention of sodium and water in NS rats receiving ANG II, but not in any other group. These results indicate that ET-1 plays a role in ANG II-induced hypertension via activation of ET(A) receptors and that this role is more prominent in rats on HS.

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We showed recently that endothelin (ET)A receptors are involved in the salt sensitivity of ANG II-induced hypertension. The objective of this current study was to characterize the role of endothelin ETB receptor activation in the same model. Male rats on fixed normal (2 meq/day) or high (6 meq/day) salt intake received a continuous intravenous infusion of ANG II or salt only for 15 days. During the middle 5 days of the infusion period, rats were given either the selective ETB receptor antagonist A-192621 or the nonselective endothelin receptor antagonist A-182086 (both at 24 mg x kg(-1) x day(-1) intra-arterially). Infusion of ANG II caused a greater rise in arterial pressure in rats on high-salt intake. The administration of A-192621 increased arterial pressure further in all rats. The chronic hypertensive effect of A-192621 was not significantly affected by salt intake or ANG II. The administration of A-182086 lowered arterial pressure chronically only in rats on normal salt intake receiving ANG II. Thus the salt sensitivity of ANG II-induced hypertension is not caused by changes in ETB receptor function.

Abstract-Long-term administration of a subpressor dose of angiotensin II (Ang II) leads to pressor hyperresponsiveness and slow development of hypertension. Our preliminary data show that mRNA expression for calcitonin-gene related peptide in dorsal root ganglia was significantly increased by subpressor infusion of Ang II. To determine the role of sensory nerves in the development of hypertension induced by subpressor infusion of Ang II, newborn Wistar rats were given 50 mg/kg SC capsaicin on the 1st and 2nd days of life. After the weaning period, male rats were divided into 4 groups and subjected to the following treatments for 2 weeks: capsaicinϩAng II (150 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 SC by osmotic pumps, CAP-AII), capsaicinϩvehicle (CAP), controlϩAng II (CON-AII), and controlϩvehicle (CON). The results show that mean arterial pressure was significantly elevated in both Ang II-infused rats compared with non-Ang II-treated rats (PϽ0.05), and it was higher in CAP-AII than in CON-AII rats (PϽ0.05). The 24-hour urinary and sodium excretions were lower in CAP-AII than in CON-AII, CAP, and CON rats (PϽ0.05). These data demonstrated that sensory denervation exacerbates the development of hypertension and impairs renal excretory function when a subpressor dose of Ang II is given. These results indicate that activation of sensory nerves, either by Ang II or by other hormonal or hemodynamic factors, plays a compensatory role in promoting urine and sodium excretion and attenuating elevated blood pressure initiated by Ang II. (Hypertension. 2000;36:549-552.) Key Words: Angiotensin II Ⅲ peptides Ⅲ hypertension, experimental I t is now clear that acute elevation of blood pressure induced by administration of pressor doses of Angiotensin (Ang) II is mainly caused by increased aldosterone production, salt and water retention, and resetting of the baroreceptor that results in increased sympathetic tone. [1][2][3][4][5][6] In addition, acute elevation of blood pressure has been shown to trigger compensatory mechanisms, for example, natriuresis and the local production of prostaglandins, 7,8 which may attenuate the increase in blood pressure induced by pressor doses of Ang II. In contrast, the slow development of hypertension induced by long-term administration of subpressor doses of Ang II mimics the development of human hypertension to a greater extent than the administration of pressor doses. During the developmental stage of hypertension, altered aldosterone levels and salt and water retention cannot be detected. 8 -12 Although intensive research has been conducted in this area, mechanisms underlying subpressor Ang II-induced hypertension are largely unknown.There is evidence showing that the renin-angiotensin system interacts with sensory nerves to modulate cardiovascular function. 13 Sensory afferent nerves have cell bodies located in the dorsal root ganglia (DRG) and extend their processes to a variety of tissues including renal tubules, resistance arteries, and heart. It has been established that sensory afferent fibers releas...

The antihypertensive effects of thiazide diuretics are not due exclusively to volume depletion. We propose that salt and water loss caused by TCM may lower MAP by impairment of salt-sensitive pressor mechanisms activated by angiotensin II.