Unveiling the Role of Multidrug Resistance Proteins in Hypertension

Abstract

H ypertension is a chronic condition associated with an increased risk of mortality and morbidity. It is estimated to cause 4.5% of current global disease burden, and its prevalence is similar in both developing and developed countries. 1 According to a recent review, Ϸ54% of stroke, 47% of ischemic heart disease, 75% of hypertensive disease, and 25% of other cardiovascular disease worldwide can be attributable to high blood pressure. 2 Altered levels of angiotensin and aldosterone are common findings in hypertension. Aldosterone has been shown to play an important role in the pathophysiology of numerous cardiovascular disorders, including heart failure and hypertension, 3 and the renin-angiotensin-aldosterone system is currently an important target for 5 antihypertensive drug classes: ␤-blockers, renin inhibitors, angiotensin-conversion enzyme inhibitors, angiotensin receptor blockers, and aldosterone antagonists. 4 In the last few years, increasing evidence has pointed to an involvement of multidrug resistance (MDR)-related proteins with hypertension. Both ABCB1 (P-glycoprotein) and ABCC1 (MDR-associated protein 1), the 2 main proteins first described in multidrug-resistant tumors, are known to physiologically transport several endobiotics, including hormones. 5,6 Moreover, ABCB1 and ABCG2 (the third protein related to MDR), seem to also be related to the secretion of several drugs to urine, including some antihypertensives. 7,8 This review summarizes the recent findings regarding the relationship between MDR-related proteins and hypertension. ABC Superfamily and MDR in CancerMDR is still the main cause of failure in cancer chemotherapy. Although it is a multifactorial phenomenon, virtually all MDR cells present an ATP-dependent reduction in intracellular drug accumulation because of the overexpression of Ն1 of 3 proteins belonging to the ATP-binding cassette (ABC) family of transporters. 9,10 The ABC superfamily is one of the largest protein families, and its members have been found in virtually all organisms examined up to now. It is consisted of 7 subfamilies, ABCA, ABCB, ABCC, ABCD, ABCE, ABCF, and ABCG, in which each protein receives a number, eg, ABCA1, ABCC7, or ABCG2. The majority of the ABC proteins are membrane transporters that actively translocate a wide range of substrates to various cellular compartments using ATP hydrolysis, which may explain the many functions fulfilled by these proteins in different organisms.The first ABC protein related to MDR was initially named P-glycoprotein and subsequently MDR1, with P being a reference for an apparent altered membrane permeability conferred by its overexpression. 11 This protein is now called ABCB1, meaning that it is the first member of the B subgroup of the ABC superfamily. The second MDR-related protein was discovered 16 years later and was called MDRassociated protein, 12 or MDR-associated protein 1, and is now renamed ABCC1. The third important MDR-related protein, now called ABCG2, was discovered almost simultaneously by 3 distinct groups, receiv...

Obstructive sleep apnea and cognitive impairment: Addressing the blood–brain barrier

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Inhibitors of N-glycosylation as a potential tool for analysis of the mechanism of action and cellular localisation of glycoprotein P.

“…P-gp can be found in endothelial cells of blood vessels in the brain where it is responsible for maintaining of the blood-brain barrier (Annese et al, 2006). In healthy tissues this protein is responsible for transport of hormones such as aldosterone and glucocorticoids, and other endogenous molecules (Delou et al, 2009). The overexpression of P-gp can be detected in malignant cells of different origin (kidney tumour, neoplasms of liver, pancreas, intestines, adrenal glands and breast, endothelial cells of newly established capillaries in tumour tissue) (Sorokin et al, 1999).…”

Ouabain-induced alterations in ABCB1 of mesenteric lymph nodes and thymocytes of rats and mice

“…Ouabain is known to modulate the expression of two ATPases associated with cancer resistance, ABCB1 and ABCC1 (47). Therefore, the present study aimed to assess whether ouabain could alter the expression or activity of ABCB1 in PBMC and thymocytes in vivo.…”