**3.4 Sympathetic Nervous System and Renal Dopaminergic System**

The Sympathetic Nervous System activity is increased in CKD, as was demonstrated almost 20 years ago (Converse et al., 1992). Afferent signals from the diseased kidney are transmitted to the vasomotor control center in the brain increasing the blood pressure (Rump et al, 2000). In addition, increased plasma noradrenaline levels are often high in CKD patients. Evidence for the role of sympathetic nervous system is provided by the fall of blood pressure after renal sympathetic denervation or after bilateral nephrectomy (Khawaja et al, 2011).

Dopamine, a precursor of noradrenaline, has a natriuretic effect by inhibiting Na-K-ATPase in proximal tubular segments. Patients with CKD have reduced urinary excretion of dopamine (Casson et al, 1983) and decreased activity of the renal dopaminergic system, which correlates well with the degree of renal dysfunction (Pestana et al, 2001). These data show that the reduced activity of renal dopaminergic system in CKD, by decreasing the sodium excretion, may be another factor connected with the hypertension of CKD.

#### **3.5 Miscellaneous**

Endothelin is a family of four 21 amino acid peptides and ET-1, the predominant isoform, is produced by endothelial cells. It can mediate vasoconstriction when binds to its A and B receptors in vascular smooth muscle cells. Vasodilation results from the interaction with the B receptor in endothelial cells. In CKD, endothelin levels are increased and the use of selective endothelin A receptor antagonist produces reduction of blood pressure associated with renal vasodilatation (Goddard et al, 2004).

Parathormone starts to rise early in CKD. Its role in the pathogenesis of hypertension remains controversial. It has been shown, by some but not all authors that the parathormone can increase intracellular calcium and aggravate hypertension and that parathyroidectomy may improve blood pressure control.

The role of Endogenous Digitalis–like Factors (EDLFs) in sodium or volume dependent hypertension was elucidated only recently, after several decades of intense research. The EDLFs include quite a few substances, produced in the adrenal gland or in the hypothalamus, that inhibit the Na-K-ATPase in cell membranes, being at the same time natriuretic and vasoconstrictors (Takahashi et al, 2011). The high levels of EDLFs in CKD

such as catalase, superoxide dismutase and glutathione dismutase (Vaziri et al., 2002). The excess of reactive oxygen species may directly stimulate vascular contraction or reduce nitric oxide, contributing to hypertension in CKD (Hu et al., 1998). In addition, it is known that anti-oxidant agents can reduce the blood pressure in animal models of hypertension (Vaziri et al., 1997). The endothelial-derived nitric oxide has the capacity to maintain the vascular tone and to produce vasodilatation, through the activation of guanylate cyclase. In CKD, there is an increase of asymmetric dimethylarginine, an inhibitor of nitric oxide synthase (Leone et al., 1992). Moreover, has we pointed out before, the increase amount of reactive oxygen species in CKD impair nitric oxide effects. These two factors are responsible for a decrease nitric oxide activity in CKD which contribute to endothelial dysfunction and

The Sympathetic Nervous System activity is increased in CKD, as was demonstrated almost 20 years ago (Converse et al., 1992). Afferent signals from the diseased kidney are transmitted to the vasomotor control center in the brain increasing the blood pressure (Rump et al, 2000). In addition, increased plasma noradrenaline levels are often high in CKD patients. Evidence for the role of sympathetic nervous system is provided by the fall of blood pressure after renal sympathetic denervation or after bilateral nephrectomy (Khawaja

Dopamine, a precursor of noradrenaline, has a natriuretic effect by inhibiting Na-K-ATPase in proximal tubular segments. Patients with CKD have reduced urinary excretion of dopamine (Casson et al, 1983) and decreased activity of the renal dopaminergic system, which correlates well with the degree of renal dysfunction (Pestana et al, 2001). These data show that the reduced activity of renal dopaminergic system in CKD, by decreasing the

Endothelin is a family of four 21 amino acid peptides and ET-1, the predominant isoform, is produced by endothelial cells. It can mediate vasoconstriction when binds to its A and B receptors in vascular smooth muscle cells. Vasodilation results from the interaction with the B receptor in endothelial cells. In CKD, endothelin levels are increased and the use of selective endothelin A receptor antagonist produces reduction of blood pressure associated

Parathormone starts to rise early in CKD. Its role in the pathogenesis of hypertension remains controversial. It has been shown, by some but not all authors that the parathormone can increase intracellular calcium and aggravate hypertension and that parathyroidectomy

The role of Endogenous Digitalis–like Factors (EDLFs) in sodium or volume dependent hypertension was elucidated only recently, after several decades of intense research. The EDLFs include quite a few substances, produced in the adrenal gland or in the hypothalamus, that inhibit the Na-K-ATPase in cell membranes, being at the same time natriuretic and vasoconstrictors (Takahashi et al, 2011). The high levels of EDLFs in CKD

sodium excretion, may be another factor connected with the hypertension of CKD.

**3.4 Sympathetic Nervous System and Renal Dopaminergic System** 

increased blood pressure.

et al, 2011).

**3.5 Miscellaneous** 

with renal vasodilatation (Goddard et al, 2004).

may improve blood pressure control.

(Hamlyn et al, 1996; Komiyama et al, 2005), secondary to an increased sodium content and expanded blood volume, may also contribute to the hypertension commonly seen in this population.
