Novel signaling pathways contributing to vascular changes in hypertension.
In hypertension, increased peripheral resistance maintains elevated levels of arterial blood pressure. The increase in peripheral resistance results, in part, from abnormal constrictor and dilator responses and vascular remodeling. In this review, we consider four cellular signaling pathways as possible explanations for these abnormal vascular responses: (1) augmented signaling via the epidermal growth factor receptor to cause remodeling of the cerebrovasculature; (2) reduced sphingolipid signaling leading to blunted vasodilation and increased smooth muscle proliferation; (3) increased signaling via Rho/Rho kinase leading to enhanced vasoconstriction, and (4) a relative state of microtubular depolymerization favoring vasoconstriction in hypertension. These novel cell signaling pathways provide new pharmacological targets to reduce total peripheral vascular resistance in hypertension.
Johns
D G
DG
Department of Physiology, Medical College of Georgia, Augusta, GA 30912-3000, USA.
Dorrance
A M
AM
Leite
R
R
Weber
D S
DS
Webb
R C
RC
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology; D002518:Ceramides / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000209:etiology / Q000503:physiopathology; D004815:Epidermal Growth Factor / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology*; D008870:Microtubules / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D051381:Rats; D015398:Signal Transduction; D013107:Sphingolipids / Q000502:physiology; D014655:Vascular Resistance; D014661:Vasoconstriction; D014664:Vasodilation; D020741:rho GTP-Binding Proteins / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000502:physiology
D002518:Ceramides; D013107:Sphingolipids; D000804:Angiotensin II; D004815:Epidermal Growth Factor; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein