Interaction of cadmium with atrial natriuretic peptide receptors: Implications for toxicity

The Effects of Short-Term Nifedipine Treatment on Responsiveness of Aortic Rings of Cadmium-Hypertensive Rats

“…production after stimulation with ET-1 was found to be decreased in aorta of DOCA-salt (33) and spontaneously hypertensive rats (34) and it was suggested that this could underlie the decreased responses to ET-1 (34). Cadmium was shown to inhibit the binding of ET-1 (36) and NA (37) to their receptors and cause alterations in receptor function with resultant changes in ligand binding (38). Cadmium was shown to inhibit the binding of ET-1 (36) and NA (37) to their receptors and cause alterations in receptor function with resultant changes in ligand binding (38).…”

Role of Cadmium-Induced Lipid Peroxidation in the Kidney Response to Atrial Natriuretic Hormone

“…Indeed, a lack of vascular response to ANP injection in the present study is in agreement with a decreased receptor affinity as well as with the results of Mikhaleva et al [8] who noted an elevated vascular resistance despite an increased ANP level in Cd-treated rats. The mechanism by which Cd causes an increase in the vascular resistance as reported by Mikhaleva et al [8] or a decrease in receptor affinity to vasodilator hormones such as ANP [10] is not reliably known, but can be attributed to a Cd-induced peroxidative damage of the cell membrane [18][19][20][21], The role of a peroxidative damage in the impaired cell response to hor mones has not been previously studied in Cd-mediated hypertension. As reported previously [22], the overall effect of peroxidative damages is to decrease the mem brane fluidity and to destabilize the membrane receptors.…”

“…Giridhar et al [10] and others [18.34] indicated that Cd-mediated changes in ANP receptor density and affinity may have a causal role in the development of hypertension. Indeed, a lack of vascular response to ANP injection in the present study is in agreement with a decreased receptor affinity as well as with the results of Mikhaleva et al [8] who noted an elevated vascular resistance despite an increased ANP level in Cd-treated rats.…”

“…The results concerning the measurement of hormone levels involved in the regulation of blood pressure failed to explain the mechanism of Cd-induced blood pressure elevation [8,9,11,13]. Among many explanatory attempts, the results of Giridhar et al [10] who showed a substantial reduction in both density and affinity of receptors for atrial natriuretic peptide (ANP) in Cd-exposed cells are very important to clarify the devel opment of Cd-induced hypertension. This diminished response to ANP may be involved in Cd-mediated blood pressure elevation, since this hormone binding to two receptors (ANP receptors A and B) on the surface of the cells decreases the responsiveness of vascular smooth muscle cells to many vasoconstrictor substances such as vasopressin and angiotensin II [14], besides inhibiting their secretion.…”

“…Despite the lack of direct evidence about deleterious effects of Cd-induced free radicals on the hormone-receptor relationship, the above mentioned implies that oxidant stress induced destabilizing in mem brane receptors may result in changes of the responsive ness of cells to hormones acting through membrane recep tors and that an oxidant stress mediated altered response of vascular bed to hormones may be involved in Cdinduced hypertension. The consequences of Cd-mediated reduction in density and affinity of ANP receptors [10] leading to a decrease in ANP response and an increase in vasoconstrictor activity of the vascular bed may facilitate the occurrence of hypertension. Despite this, the involve ment of lipid peroxidation in the response to ANP, a welldefined vasodilator hormone, has not been studied in Cdinduced hypertensive rats before.…”