Vascular beta-adrenoceptor-mediated responses in hypertension and ageing in rats

J Auton Pharmacol. 1992 Dec;12(6):389-401. doi: 10.1111/j.1474-8673.1992.tb00387.x.

Abstract

1. In normotensive Wistar (W) and spontaneously hypertensive (SHR) rats between 5 and 20 weeks of age, there was an age-related increase in blood pressure (r2 = 0.770 and r2 = 0.801 respectively). Except for adrenaline (r2 = 0.979) in SHRs, plasma catecholamines and age were unrelated. 2. In ring segments of thoracic aorta from 5, 10, 15 and 20 week old rats, the respective EC80s (-log M) for phenylephrine (PE)-induced contractions were 8.20 +/- 0.37, 7.96 +/- 0.10, 7.15 +/- 0.12 and 7.12 +/- 0.21 in W and 7.73 +/- 0.13, 7.72 +/- 0.16, 7.37 +/- 0.08 and 7.40 +/- 0.03 in SHR tissues (means +/- SEM; n = 5-7). 3. In PE-preconstricted rings, the respective EC50s (-log M) for isoprenaline (IPNA)-induced relaxation were 7.97 +/- 0.11, 7.74 +/- 0.10, 6.96 +/- 0.19 and 6.57 +/- 0.26 in W and 8.03 +/- 0.24, 7.62 +/- 0.08, 6.88 +/- 0.13 and 6.73 +/- 0.14 in SHR tissues (n = 5-7). 4. In PE-preconstricted rings from 5 and 20 week old rats, a single concentration of IPNA (approximating the respective IPNA EC50s) induced relaxation which was sustained over 2 h in W but not SHR tissues. The SHR:W ratios of the net relaxant responses, at 5 and 20 weeks, were 0.6461 and 0.6167 respectively. 5. Thus, W rats exhibit an age-related loss in both vascular alpha- and beta-adrenoceptor responsiveness which appears unrelated to plasma catecholamines. SHRs also exhibit an age-related loss in vasodilator beta-adrenoceptor responsiveness, which may involve adrenaline-induced desensitization, but appear to maintain vasoconstrictor alpha-adrenoceptor responsiveness. It is proposed that an age-related decline in beta-adrenoceptor responsiveness coupled to maintenance of alpha-adrenoceptor responsiveness may lead to chronic blood pressure elevation, as observed in SHRs, while a parallel decline in both alpha- and beta-adrenoceptor responsiveness, as observed in W rats, may preclude hypertension development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Aorta, Thoracic
  • Blood Pressure / drug effects
  • Hypertension / physiopathology*
  • Isoproterenol / pharmacology*
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Norepinephrine / blood
  • Phenylephrine / pharmacology*
  • Rats
  • Rats, Inbred SHR
  • Rats, Wistar
  • Receptors, Adrenergic, alpha / physiology
  • Receptors, Adrenergic, beta / physiology*
  • Vasoconstriction / drug effects
  • Vasodilation / drug effects

Substances

  • Receptors, Adrenergic, alpha
  • Receptors, Adrenergic, beta
  • Phenylephrine
  • Isoproterenol
  • Norepinephrine