OBJECTIVE To investigate whether a dietary supplement of vitamin B6 could attenuate the elevation of systolic blood pressure (SBP) in Zucker obese or spontaneously hypertensive rats, or rats ingesting sucrose. METHODS Zucker obese rats (fa/fa), Sprague-Dawley rats with sucrose-induced elevation of SBP, spontaneously hypertensive rats (SHRs) and their corresponding controls were tested for the effects of vitamin B ingestion in different ways: (1) vitamin B6 was included as a supplement (five times the normal intake) from the start of the experiment until the development of hypertension; (2) vitamin B6 supplement was removed from the diet of Zucker obese and Zucker lean control groups after 16 weeks on the dietary treatments; and (3) a diet deficient in vitamin B6 was instituted in SHRs and control Wistar-Kyoto (WKY) rats. The SBP of rats in all groups was monitored in the conscious animal by tail-cuff plethysmography. The effects of the various treatments on the uptake of calcium by caudal artery segments were examined. RESULTS Male Zucker obese rats (fa/fa) of age 6 weeks fed a commercial rat chow developed hypertension in 3-4 weeks, whereas their lean controls (Fa/Fa) did not. The inclusion of a vitamin B6 supplement (five times the normal intake) resulted in a complete attenuation of the hypertension in the obese strain. Removal of the vitamin B6 supplement from the diet of these obese rats resulted in the return of hypertension within 2 weeks. Similar changes in SBP were also observed in the Zucker lean controls treated with vitamin B6. The ingestion of sucrose by male Sprague-Dawley rats resulted in modest elevation of SBP that was attenuated by the inclusion of the vitamin B6 supplement in their diet. In contrast, there was no response to the inclusion or removal of dietary vitamin B6 supplement in the SHRs. However, the WKY control rats responded to both these conditions in a similar manner to that seen in the Sprague-Dawley strain. Increased peripheral resistance resulting from increased permeability of vascular smooth muscle plasma membrane to Ca2+ is thought to be one of the mechanisms of hypertension. Changes in SBP correlated with changes in the uptake of calcium by caudal artery segments in all the groups studied. The Zucker obese and sucrose-induced hypertensive rats have abnormalities in carbohydrate metabolism. The vitamin B6 supplement decreased the random or fasting blood glucose levels in the Zucker obese and sucrose-fed rats respectively. CONCLUSIONS This is the first observation that animal models of hypertension can be classified on the basis of their response to a vitamin B6 supplement. On this basis, the etiology of hypertension in SHRs is quite distinct from that in Zucker obese rats and in rats ingesting sucrose.