Characterisation of vasopressin V(1A), angiotensin AT(1) and AT(2) receptor distribution and density in normotensive and hypertensive rat brain stem and kidney: effects of restraint stress.
In the present study, we have examined neurochemical correlates that may be involved in the differential cardiovascular responses observed in normotensive and hypertensive rats during stress. Using a restraint stress paradigm, both normotensive Wistar Kyoto (WKY) and Spontaneously Hypertensive rats (SHR) underwent acute (1 h restraint in a perspex tube), chronic (1 h restraint for ten consecutive days) or no restraint (control) stress. Following cessation of restraint, rats were processed by incubating sections of brain stem and kidney with [125I]-HO-LVA (0.03 nM) or [125I]Sar(1)Ile(8)-AngiotensinII (0.5 nM), in the presence of PD123319 (10 microM) or losartan (10 microM), to determine the distribution and density of vasopressin V(1A), angiotensin AT(1) and AT(2) receptors, respectively. Analysis of autoradiograms indicated changes in the density of radioligand binding in acutely and chronically-stressed rats, as compared to controls. For example, V(1A) binding in the medial nucleus tractus solitarius (SolM) decreased in the WKY but increased in the SHR. AT(1) binding in SolM did not significantly change in the WKY but decreased in the SHR with repeated restraint. In kidney slices, AT(1) binding decreased with stress in the WKY (-17%) but increased in SHR (+10-15%). AT(2) binding in the kidney showed a pattern similar to that of AT(1) binding in SHR, but not WKY. Graded increases in V(1A) binding were measured in kidney medulla and cortex of both strains (+50-60% with chronic restraint). These results suggest that physiological adaptation to restraint is associated with specific changes in V(1A), AT(1) and AT(2) receptor density within brain nuclei and kidney.
McDougall
S J
SJ
Department of Pharmacology, Monash University, Wellington Rd., Victoria, 3168, Clayton, Australia.
Roulston
C A
CA
Widdop
R E
RE
Lawrence
A J
AJ
D000208:Acute Disease; D000818:Animals; D001933:Brain Stem / Q000378:metabolism*; D002908:Chronic Disease; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism*; D017483:Receptors, Vasopressin / Q000378:metabolism*; D012016:Reference Values; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000378:metabolism*; D014018:Tissue Distribution
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin