Development of Hypertension Induced by Subpressor Infusion of Angiotensin II

Abstract

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 vanilloid receptor and hypertension1

“…We [55] found that the AT1 receptor content in the adrenal gland was not altered in any of the experimental groups, strongly suggesting that insufficiently suppressed PAL is a reflection of insufficiently suppressed circulating and/or tissue AII levels. In contrast to above mentioned studies that define the role of the RAAS in the development of hypertension in capsaicin treated rats fed a high-salt diet, we studied the role of sensory nerves in attenuating the development of hypertension induced by AII infusion [56] . AII or vehicle-infused rats were pretreated with capsaicin or vehicle.…”

Involvement of Spinal Angiotensin II System in Streptozotocin-Induced Diabetic Neuropathic Pain in Mice

“…In the RAS, angiotensinogen (AGT) is metabolized into Ang I, and Ang I is then converted to Ang II by Ang converting enzyme (ACE) (Paul et al, 2006;Campbell, 2014). The evidence indicates that Ang II, a main bioactive component of the RAS, affects a wide range of central and peripheral components of the sensory systems (Wu et al, 2000;Burkhalter et al, 2001;Pelegrini-da-Silva et al, 2005), and is mediated by Ang II type 1 (AT1) and Ang II type 2 (AT2) receptors.…”

The Characterization of AT1 Expression in the Dorsal Root Ganglia After Chronic Constriction Injury

“…There is substantial evidence that Ang II through its receptors can regulate the central and peripheral components of sensory systems (Buck et al 1982;Pelegrini-da-Silva Martins and Prado 2005;Saavedra 1992;Wu et al 2000). Recently, the presence of intraneuronal angiotensinergic system and Angiotensin II receptor type 1 (AT 1 ) has been documented in rat dorsal root ganglia (DRGs) (Patil et al 2010;Pavel et al 2008;Tang et al 2008), the structures containing primary afferent neurons that convey sensory information from periphery to the CNS.…”