Endothelin-1 and vasopressin signalling in blood vessels of young SHR in comparison to adult SHR.
To examine potential intracellular signalling abnormalities of endothelin-1 (ET-1) and vasopressin (AVP) which may contribute to blood pressure elevation, contractility and inositol phosphate levels in intact arteries and calcium transients in vascular smooth muscle cells were investigated after stimulation with these peptides in pre-hypertensive 5 week-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) rats. Contractility of aorta in response to ET-1, AVP and norepinephrine (NE) was blunted in SHR relative to WKY. Contraction of mesenteric resistance arteries induced by ET-1 was similar in both groups, whereas sensitivity in response to NE and AVP was greater in SHR. Basal inositol phosphate in aorta and mesenteric arteries was elevated in SHR, but ET-1 and AVP-stimulated inositol phosphate responses were similar in both groups. Calcium transients induced by ET-1 and AVP in vascular smooth muscle cells were similar in young SHR and WKY. In contrast, in adult rats inositol phosphate responses to ET-1 were blunted in aorta of SHR, but were normal in mesenteric arteries. Inositol phosphate responses to AVP were similar in both rat strains of rats both in aorta and mesenteric arteries except for accumulation of inositol trisphosphate, which was enhanced in mesenteric arteries of SHR. Calcium mobilization in vascular smooth muscle cells from adult SHR also exhibited enhanced responses to AVP. In conclusion, in young SHR, blunted ET-1 and AVP-induced contraction in aorta and enhanced AVP-induced mesenteric artery contraction are associated with normal inositol phosphate production and calcium mobilization. Signal transduction in response to ET-1 and AVP is depressed in aorta of pre-hypertensive SHR after the step of inositol phosphate generation and calcium mobilization. Resistance vessel reactivity to AVP is enhanced in young SHR at steps following inositol phosphate generation and calcium mobilization. These results argue against a role of ET-1, but suggest the possible involvement of AVP in the development of this model of genetic hypertension.
Yang
X P
XP
Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada.
Touyz
R M
RM
Nguyen
P V
PV
Deng
L Y
LY
Li
J S
JS
Schiffrin
E L
EL
D000375:Aging / Q000502:physiology*; D000818:Animals; D000906:Antibodies; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001794:Blood Pressure; D001835:Body Weight; D002118:Calcium / Q000493:pharmacokinetics; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000097:blood / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology; D009638:Norepinephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000096:biosynthesis / Q000493:pharmacokinetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D014316:Tritium; D010738:Type C Phospholipases / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000906:Antibodies; D019332:Endothelin-1; D010716:Phosphatidylinositols; D014662:Vasoconstrictor Agents; D014316:Tritium; D001127:Arginine Vasopressin; D010738:Type C Phospholipases; D002118:Calcium; D009638:Norepinephrine