Effect of calcium membrane blockers on in vivo vasoconstrictor properties of norepinephrine, angiotensin II and vasopressin.

In the present study the in vivo role of transcellular calcium influx in humorally-mediated vasoconstriction was examined in conscious rats using two chemically dissimilar inhibitors of cellular calcium uptake, namely verapamil (Ver, 50 micrograms/kg/min) and nifedipine (Nif, 7.5 micrograms/kg/min). The pressor effect of arginine vasopressin (AVP, 10 mU/kg/min), angiotensin II (AII, 0.3 micrograms/kg/min) and norepinephrine (NE, 4 micrograms/kg/min) was virtually abolished by Ver and Nif. None of the pressors when infused alone increased mean arterial pressure (MAP) by increasing cardiac index (CI). During the administration of the calcium antagonists and AII or NE, CI was slightly but not significantly higher than with AII or NE alone. A modest fall in CI occurred with AVP and Ver but not with AVP and Nif. Thus, the effect of calcium antagonists to block the pressor responses of AVP, NE and AII was primarily by preventing the increase in peripheral vascular resistance rather than depressing CI. In summary, transcellular calcium influx appears to constitute the common in vivo pathway for constriction of peripheral blood vessels by AVP, NE and AII. These findings have substantial pathogenetic and therapeutic implications in hypo- and hypertensive states.