Intrarenal transport and vasoactive substances in hypertension.
Blood pressure is influenced by several vasoactive factors that also regulate nephron transport. An imbalance in regulation of salt reabsorption by the nephron contributes to hypertension. In the spontaneously hypertensive rat (SHR), the responses to dopamine and angiotensin II in the proximal nephron are diminished and enhanced, respectively. This partially explains why the proximal tubule of SHR absorbs more salt and water than that of normotensive controls. In the Dahl salt-sensitive rat, defects in NO signaling and alterations in the arachidonic acid/cytochrome P450 pathways are associated with increased salt reabsorption by the thick ascending limb. In other animal models, such as the deoxycorticosterone acetate (DOCA)-salt rat, hypertension develops as the result of an induced hormonal imbalance. By mimicking the effects of aldosterone, DOCA stimulates sodium reabsorption in the collecting ducts, causing salt and fluid retention. Thus, this model is similar to inherited forms of human hypertension caused by abnormal regulation of transport by mineralocorticoids, such as apparent mineralocorticoid excess and glucocorticoid-remediable aldosteronism. Overall, these findings demonstrate the significance of vasoactive compounds in regulating nephron transport and controlling blood pressure. However, important questions regarding humoral control of nephron transport and its implications in hypertension remain unanswered, and intensive research in these areas is required.
Ortiz
P A
PA
Division of Hypertension, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan, USA.
Garvin
J L
JL
D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism*; D051381:Rats; D020303:Rats, Inbred Dahl; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D001120:Arginine