Vascular binding sites and biological activity of vasopressin in DOCA-salt hypertensive rats.
In order to understand the regulation of vascular vasopressin receptors in hypertension, vasopressin (AVP) binding sites and the pressor response to AVP in the perfused mesenteric vasculature of DOCA-salt hypertensive rats, sodium-loaded and DOCA-treated rats were investigated. The binding capacity for AVP (Bmax) was significantly reduced (P less than 0.05) in uninephrectomized, DOCA-treated rats (70 +/- 17 fmol/mg protein) and in DOCA-salt hypertensive rats (90 +/- 9 fmol/mg protein) with respect to uninephrectomized rats (130 +/- 32 fmol/mg protein) or uninephrectomized salt-loaded rats (155 +/- 47 fmol/mg protein), with no change in affinity. In these rats with lower receptor density, however, the maximal pressor response to AVP in the perfused mesenteric vascular bed was increased (P less than 0.05). In DOCA-salt hypertensive rats plasma AVP was higher than in the other groups. In similarly treated rats with intact kidneys, which therefore did not become hypertensive, receptor density was significantly decreased after combined DOCA-salt treatment, together with an exaggerated pressor response to AVP and increased plasma AVP concentrations. These results suggest that AVP receptors are down-regulated when there is an increment in the plasma concentration of AVP, although other factors may also play a role. Biological responses to AVP are, however, increased in spite of decreased receptor density and this phenomenon is independent of the elevation in blood pressure and results from an exaggerated response mediated by post-receptor mechanisms.
Larivière
R
R
Experimental Hypertension Laboratory, Clinical Research Institute of Montreal, Quebec, Canada.
St-Louis
J
J
Schiffrin
E L
EL
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000378:metabolism*; D017483:Receptors, Vasopressin; D012083:Renin / Q000097:blood
D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D003900:Desoxycorticosterone; D012083:Renin