Hypertension and kidneys: unraveling complex molecular mechanisms underlying hypertensive renal damage

Abstract

Kidney damage represents a frequent event in the course of hypertension, ranging from a benign to a malignant form of nephropathy depending on several factors, that is, individual susceptibility, degree of hypertension, type of etiology and underlying kidney disease. Multiple mechanisms are involved in determination of kidney glomerular, tubular and interstitial injuries in hypertension. The present review article discusses relevant contributory molecular mechanisms underpinning the promotion of hypertensive renal damage, such as the renin-angiotensin-aldosterone system (RAAS), oxidative stress, endothelial dysfunction, and genetic and epigenetic determinants. We highlighted major pathways involved in the progression of inflammation and fibrosis leading to glomerular sclerosis, tubular atrophy and interstitial fibrosis, thus providing a state of the art review of the pathogenetic background useful for a better understanding of current and future therapeutic strategies toward hypertensive nephropathy. An adequate control of high blood pressure, obtained through an appropriate therapeutic intervention, still represents the key strategy to achieve a satisfactory control of renal damage in hypertension. In this regard, we reviewed the impact of currently available antihypertensive pharmacological treatment on kidney damage, with particular regard to RAAS inhibitors. Notably, recent findings underscored the ability of the kidneys to regenerate and to repair tissue injuries through the differentiation of resident embryonic stem cells. Pharmacological modulation of the renal endogenous reparative process (that is, with angiotensin-converting enzyme inhibitors and AT1 angiotensin II receptor blockers), as well as future therapeutic strategies targeted to the renopoietic system, offers interesting perspectives for the management of hypertensive nephropathy.

Heavy Alcohol Consumption Effects on Blood Pressure and on Kidney Structure Persist After Long-Term Withdrawal

“…Kidneys play an integral role in blood pressure (BP) regulation and even the slightest impairment of renal function can contribute to the development of hypertension [1, 2], which remains the leading cause of morbidity and mortality worldwide [3]. Among the modifiable risk factors for the development of hypertension, heavy ethanol consumption is considered as one of the most relevant unhealthy lifestyle pattern [3, 4], and data from epidemiologic, clinical and experimental studies have provided a compelling link between these two conditions [4-10].…”

Podocyte Purinergic P2X4 Channels Are Mechanotransducers That Mediate Cytoskeletal Disorganization

“…Deeper insight into the mechanisms leading to mechanically induced podocyte damage may be instrumental in devising targeted treatments for podocyte injuries, as seen in hypertensive nephropathy. 18 …”

Mono- Or Combined Antihypertensive Therapy in Women With Arterial Hypertension and Moderate Risk of Cardiovascular Diseases: What’s Better?

“…Полученное нами снижение уровня АУ и уменьшение числа пациенток с АУ в результате адекватной, особенно комбинированной, антигипертензивной терапии отра-жает органопротективный эффект препаратов, в первую очередь блокаторов РААС, гормоны которой способству-ют изменению внутрипочечной гемодинамики и струк-турному повреждению почечной паренхимы. Вследствие гиперактивации РААС возникает стойкая вазоконстрик-ция, гипертрофия, фиброз и ремоделирование артери-альных сосудов, что приводит к поражению почечных клубочков и постепенному развитию гломерулосклеро-за [14,15]. Кроме того, вазоактивные агенты, воспале-ние, механические и метаболические факторы способ-ствуют образованию активных форм кислорода, что сопровождается снижением биодоступности оксида азота и в итоге усиливает реактивность клеток гладких мышц сосудов [16].…”