Vasoconstrictor hyperresponsiveness: an early pathogenic mechanism in the spontaneously hypertensive rat.
Factors which play a primary role in the initiation and development of hypertension in spontaneously hypertensive rats (SHR) are incompletely defined. To test the possibility that early changes in vascular function play a primary etiologic role, hindquarters of 3-week-old SHR and Wistar-Kyoto normotensive rats (WKY) were perfused at constant flow with plasma substitute. The vasculature of SHR exhibited higher resistance to flow than that of WKY. The threshold constrictor response to norepinephrine (NE) was elicited at a significantly lower concentration (6X) than required in WKY, while threshold to BaCl2 was not different. At concentrations of BaCl2 above threshold, SHR exhibited marked hyperresponsiveness compared to WKY. This resulted in a greater maximum response and thus a steeper slope. The ED50 for BaCl2 was not different. A similar dose--response relationship (greater maximum, steeper slope) was observed with NE except that the ED50 as well as threshold was significantly lower in SHR than in WKY. These data show that vasoconstrictor hyperresponsiveness and increased vascular resistance are present at the time when the hypertension is first detectable. The hyperresponsiveness includes two distinct components: (1) A specific hypersensitivity to NE and (2) non-specific hyperresponsiveness which could derive from altered excitation--contraction  coupling and/or from a structural mechanism already present when pressure differences begin to appear.
D000818:Animals; D001464:Barium / Q000494:pharmacology; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D001464:Barium; D009638:Norepinephrine