Involvement of central α1-adrenoceptors on renal responses to central moxonidine and α-methylnoradrenaline

Abstract

Moxonidine (alpha2-adrenoceptor/imidazoline receptor agonist) injected into the lateral ventricle induces diuresis, natriuresis and renal vasodilation. Moxonidine-induced diuresis and natriuresis depend on central imidazoline receptors, while central alpha1-adrenoceptors are involved in renal vasodilation. However, the involvement of central alpha1-adrenoceptors on diuresis and natriuresis to central moxonidine was not investigated yet. In the present study, the effects of moxonidine, alpha-methylnoradrenaline (alpha2-adrenoceptor agonist) or phenylephrine (alpha1-adrenoceptor agonist) alone or combined with previous injections of prazosin (alpha1-adrenoceptor antagonist), yohimbine or RX 821002 (alpha2-adrenoceptor antagonists) intracerebroventricularly (i.c.v.) on urinary sodium, potassium and volume were investigated. Male Holtzman rats (n = 5-18/group) with stainless steel cannula implanted into the lateral ventricle and submitted to gastric water load (10% of body weight) were used. Injections of moxonidine (20 nmol) or alpha-methylnoradrenaline (80 nmol) i.c.v. induced natriuresis (196 +/- 25 and 171 +/- 30, respectively, vs. vehicle: 101 +/- 9 microEq/2 h) and diuresis (9.0 +/- 0.4 and 12.3 +/- 1.6, respectively, vs. vehicle: 5.2 +/- 0.5 ml/2 h). Pre-treatment with prazosin (320 nmol) i.c.v. abolished the natriuresis (23 +/- 4 and 76 +/- 11 microEq/2 h, respectively) and diuresis (5 +/- 1 and 7.6 +/- 0.8 ml/2 h, respectively) produced by i.c.v. moxonidine or alpha-methylnoradrenaline. RX 821002 (320 nmol) i.c.v. abolished the natriuretic effect of alpha-methylnoradrenaline, however, yohimbine (320 nmol) did not change renal responses to moxonidine. Phenylephrine (80 nmol) i.c.v. induced natriuresis and kaliuresis that were blocked by prazosin. Therefore, the present data suggest that moxonidine and alpha-methylnoradrenaline acting on central imidazoline receptors and alpha2-adrenoceptors, respectively, activate central alpha1-adrenergic mechanisms to increase renal excretion.

How impaired efficacy happened between Gancao and Yuanhua: Compounds, targets and pathways

“…On the fourth day all mice except for N group were weighted and intraperitoneal injected with NS of 15% body weight 17, 52, 53 . Drinking water was revoked and the mice were immediately weighted every hour for 8 hours.…”

Renoprotective effects of prazosin on ischemia-reperfusion injury in rats

“…15 Besides that, blockade of α1-AR has been reported to reduce the effects of renal function and hemodynamic changes induced by stimulation of renal nerve and injection of norepinephrine (NE) in the kidney. 13 Therefore, the evidence has confirmed the effectiveness of α1-AR antagonists in the treatment of kidney against renal failures such as IR injury. 16…”

“…12 It has been found that alpha1adrenoceptor (a1-AR) is one of the functionally relevant adrenoceptor subtypes in the renal vasculature of the rat. 13 In fact, adrenoceptors are G protein coupled receptors, expressing in arterioles of kidney and participate in a variety of physiological renal functions and inhibition of a1-AR exhibit preventing impact on renal injury. 14 Several lines of studies have demonstrated that blocking of a1-AR decreases the level of stressinduced pro-inflammatory cytokines such as IL-1, IL-6 and increases the production of anti-inflammatory factors such as IL-10.…”

“…12 It has been found that alpha1-adrenoceptor (α1-AR) is one of the functionally relevant adrenoceptor subtypes in the renal vasculature of the rat. 13…”

Induction of renal artery hyperresponsiveness by alpha1-adrenoceptor in hepatorenal syndrome

“…It has been suggested that alpha1-adrenoceptor (α1-AR) is the functionally relevant adrenoceptor subtype in the renal vasculature of the rat. Additionally, α1-AR blockade has been reported to attenuate renal hemodynamic and functional changes induced by renal nerve stimulation and norepinephrine (NE) injection in the kidney [ 8 ]. Concurrent administration of α1-AR antagonists (prazosin and losartan) mitigated the fall in renal hemodynamics of ARF rats, although the effects of prazosin on renal function were not examined after ischemia reperfusion [ 9 ].…”