Effect of alpha 1-adrenoceptor blockade on the development of hypertension in the spontaneously hypertensive rat.
There is a large body of evidence to suggest that the sympathetic nervous system plays a critical role in the development of hypertension and vascular medial hypertrophy in the spontaneously hypertensive rat (SHR). The synthesis of a water soluble, specific alpha 1-adrenoceptor antagonist (terazosin) has permitted an examination of the influence of alpha 1-adrenoceptors on those two phenomena. Thus, in the present study, terazosin (43 mg/kg per day) was administered to SHR and Wistar-Kyoto (WKY) rats from 4.5 to 12 weeks of age, and a number of assessments made in vitro and in vivo. In the SHR, the development of hypertension was not prevented by terazosin. The drug did not influence blood pressure in the WKY. This was despite the fact that animals which had been chronically treated with terazosin displayed marked alpha-adrenoceptor blockade in vivo. The response of systolic blood pressure to tyramine and noradrenaline was significantly reduced in animals which had been chronically treated with terazosin. In both the SHR and WKY, chronic administration of terazosin did not influence vascular concentrations of 3-methylhistidine, a biochemical marker for contractile proteins and vascular medial hypertrophy. The results therefore argue against a role of alpha 1-adrenoceptors in the development of hypertension and vascular medial hypertrophy in the SHR.
Department of Clinical and Experimental Pharmacology, University of Adelaide, Australia.
J R
JR
Jonsson
R J
RJ
Head
D B
DB
Frewin
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008762:Methylhistidines / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D011224:Prazosin / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000317:Adrenergic alpha-Antagonists; D015415:Biomarkers; D008762:Methylhistidines; C041226:Terazosin; C028118:3-methylhistidine; D011224:Prazosin