Altered renin release and propranolol potentiation of vasodilatory drug hypotension.
Vasodilating antihypertensive drugs induce hypotension with reflex tachycardia, renin release, and fluid and electrolyte retention. Propranolol can impair this renin release. The studies described here were designed to determine the hemodynamic role of vasodilatory drug-induced renin release and inhibition thereof by propranolol in two animals models, the unanesthetized, normotensive and the unanesthetized, genetically hypertensive rat. In studies with normotensive rats, propranolol impaired renin release and tachycardia resulting from hydralazine and minoxidil and potentiated their hypotensive action. Two additional interventions against the renin-angiotensin system were used in evaluating the mechanism of this potentiation. One was removal of the renin source by nephrectomy, and the second was blockade of angiotensin's vasoconstrictor action using a selective angiotensin antagonist, saralasin (1-Sar-8-Ala-angiotensin II (previously known as P113)).. Both interventions potentiated vasocilatory drug hypotension, as did propranolol, but did not prevent reflex tachycardia. When combined with saralasin propranolol did not add to protentiation by this peptide. A similar pattern of blood pressure decrement and potentiation was seen in genetically hypertensive rats when propranolol or saralasin treatment preceded hydralazine. Propranolol was demonstrated to block hydralazine-induced increases in serum renin activity in genetically hypertensive rats. We conclude that hypotensive potentiation of vasocilating drugs by propranolol in these animal models is mediated to a large extent by impairment of renin release. Persistence of hypotensive tachycardia after nephrectomy and after saralasin in normotensive rats suggests the irrelevance of angiotensin's central nervous system stimulation to this cardiac effect. Clinical studies are underway to quantify the potential importance of this beneficial drug interaction in man.
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics; D006830:Hydralazine / Q000008:administration & dosage / Q000494:pharmacology; D007022:Hypotension / Q000139:chemically induced; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D008914:Minoxidil / Q000008:administration & dosage / Q000494:pharmacology; D009392:Nephrectomy; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D012083:Renin / Q000097:blood / Q000378:metabolism*; D013610:Tachycardia / Q000139:chemically induced; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D000804:Angiotensin II; D006830:Hydralazine; D008914:Minoxidil; D011433:Propranolol; D012083:Renin