Role of extracellular calcium in isometric contractions of the SHR aorta. Influence of age and antihypertensive treatment.

Isometric contractions induced by noradrenaline (NA), 1.8 X 10(-5) M or by potassium (K+), 127 mM were studied in paired ring-preparations of the thoracic aortae from spontaneously hypertensive rats (SHR) and age-matched normotensive Kyoto-Wistar rats. In rats aged 8--16 weeks, NA-induced contractions were significantly more dependent on extracellular calcium in preparations from the SHR than from the NWR, whereas K+induced contractions showed no difference. Relaxation studies revealed differences between SHR and NWR also in K+-induced contractions. Comparison of responses in NWRs aged 3--4 months and 10--12 months showed a significant increment in Ca++-dependency with age. This age-related difference was less pronounced in SHRs, but the effect of blockade of Ca++-influx by nifedipine was significantly stronger in the old than in the young SHR-aorta. Treatment with propranolol or hydrochlorothiazide + timolol + minoxidil for 4--5 months caused no significant reduction of blood pressure and no change in Ca++-dependency. In contrast, treatment with verapamil (60 mg/kg/day) for 12 months resulted in a significantly lower blood pressure in the treated SHRs than in their controls. A trend towards "nomrlization" of the Ca++-dependency in verapamil treated rats was also observed. The results suggest that an increased Ca++-dependency in the SHR aortae is present already at the age of 8--16 weeks, but becomes more pronounced with age. As an age-related increment in Ca++-dependency is also found in NWRs, the results suggest that the SHR aortae are "functionally" older than the NWR vessels already in young animals. Calcium antagonists seem to be effective in lowering blood pressure in SHRs and represent a promising approach to the treatment of hypertensive vascular disease.