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Biomedical subjects

H C Mitchell

Publications and source records attributed to H C Mitchell.

29 records · Page 2Linked to original sources
PubMed1977

Clonidine and the vasodilating beta blocker antihypertensive drug interaction.

Because propranolol is contraindicated in some patients and since clonidine can decrease heart rate and renin release, clonidine was substituted for propranolol in 14 severely hypertensive minoxidil-treated outpatients. Clonidine induced weight loss which, since plasma concentrations were not suppressed, was not due to inhibition of release of antidiuretic hormone or renin. These endocrine interrelations were confirmed by later administration of clonidine to 4 of the subjects under controlled circumstances in our General Clinical Research Center. When substituted for propranolol, clonidine controlled blood pressure and heart rate in 8 of the 9 outpatients whose blood pressure had been previously well controlled. Clonidine and propranolol had additive antihypertensive effects in the other 5 patients. Thus, clonidine can substitute for propranolol or when added to the propranolol-vasodilator combination supply an additional blood pressure-lowering effects. This substitution or addition results in an increase in side effects. In addition, clonidine has a diuretic action under these circumstances by an unknown mechanism.

Adrenergic beta-Antagonists↗
PubMed1976

Additive effect of beta-adrenergic blockers in combination with vasodilators in lowering blood pressure.

Complications of hypertension are by far the greatese preventable public health problem in many of the developed countries of the world. Pharmacologic interventions which primarily involve drug interactions are the generally available and effective means of preventing or delaying these hypertensive complications. Mechanisms of beneficial antihypertensive drug interactions involve simultaneous reduction or control of blood volume (diuretic agents) and decrease of peripheral resistance. Reduction of peripheral resistance without producing intolerable side effects has recetnly been achieved by a complex drug interaction. This interaction involves simultaneous vasodilation and inhibition by beta-adrenergic blocking agents of reflex activation of the renin-angiotensin axis. Clonidine, by effects similar to propranolol, can substitute for propranolol in some patients, or add to the beneficial effects of this important drug interaction.

Adrenergic beta-Antagonists↗
PubMed1976

Angiotensin antagonists as diagnostic and pharmacologic tools.

Angiotensin antagonists have become useful tools in studying pharmacologic and pathophysiologic roles of the renin-angiotensin axis. Several of these uses are described herein. Their value as t-ols in the diagnosis of renal artery stenosis is yet to be determined.

Aldosterone↗
PubMed1976

Clinical pharmacology of angiotensin antagonists.

The early clinical pharmacologic investigations of saralasin were facilitated by the availability of a highly sensitive and specific radioimmunoassay for this peptide. In these studies, plasma concentrations of saralasin were correlated with inhibition of angiotensin receptors in each of three organ systems: vascular smooth muscle, adrenal cortex, and the renin release control mechanism in the kidney. The biochemical half-life of plasma saralasin was 3.2 min and an infusion time-to-plateau was 12--15 min. Saralasin inhibited adrenal cortical, vascular, and intrarenal (renin release) angiotensin receptors. The time required for manifesting these blocking actions was short(3--10 min) except for the 30--60 min required to suppress plasma aldosterone. Saralasin-induced blood pressure lowering was dependent on previously elevated serum renin activity and volume depletion. Expansion of intravascular volume prevented hypotensive responses to saralasin even in high-renin patients. Saralasin-induced renin release occurred independent of hypotension and could be inhibited by propranolol, a beta-adrenergic blocking agent. Thus, saralasin is a selective angiotensin antagonist which lacks organ specificity. It is a highly useful tool in pharmacologic studies of the renin--angiotensin axis in man and shows promise as a diagnostic tool.

Aldosterone↗
PubMed1975

Renin release, saralasin and the vasodilator-beta-blocker drug interaction in man.

Saralasin, an angiotensin antagonist, was used to study the role of renin-angiotensin in the vasodilator-beta-blocker drug interaction in hypertensive subjects. Plasma renin activity was elevated by withdrawal of propranolol in seven patients using minoxidil and propranolol. After propranolol withdrawal, saralasin caused hypotension (100/60 mm Hg or less) in five. Propranolol lowered blood pressure and plasma renin activity and diminished the hypotensive response to saralasin. Saralasin induced renin release in all patients, an effect blocked by propranolol. We conclude that angiotensin can be the major determinant of blood pressure in vasodilator-drug treated patients, that propranolol lowering of blood pressure in this vasodilator-beta-blocker drug interaction is related to suppression of renin release, and that the angiotensin feed-back-suppression mechanism for inhibiting renin release in functionally located proximal to beta-adrenergic receptors mediating renin release.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

The hypernoradrenergic state in vasodilator drug-treated hypertensive patients: effect of clonidine.

We studied 11 previously refractory hypertensive subjects who were treated with minoxidil, propranolol, and diuretics for 2--7 years. During this time 70 random blood samples were collected in the supine position and analyzed for plasma norepinephrine (PNE) and plasma renin activity (PRA). The mean PNE was 546 pg/ml (normal mean +/- SE, 173 +/- 10) and was reciprocally related to log PRA. To determine if this elevated PNE would respond to clonidine, 5 of the patients were admitted to the General Clinical Research Center for administration of placebo and later of clonidine (0.1 or 0.2 mg). A single dose of clonidine suppressed PNE (p less than 0.01) and lowered mean blood pressure (p less than 0.02) for 12 hr. The PRA was not altered significantly by clonidine. Thus, high PNE in these treated patients can be suppressed by clonidine, and this suppression of PNE and blood pressure occurs without alteration of PRA.

Adult↗
PubMedDate not supplied

Dose-response of clonidine on plasma catecholamines in the hypernoradrenergic state associated with vasodilator beta-blocker therapy.

Six patients receiving minoxidil, propranolol, and diuretics had clonidine added in increasing dosage. Five patients received 0.2-0.8 mg/day clonidine and one patient 0.2-0.6 mg. Plasma catecholamines, renin activity, blood pressure, and serum creatinine were measured at each dose level. The patients had a hypernoradrenergic state prior to clonidine [mean +/- SE plasma norepinephrine (PNE), 924 +/- 141 pg/ml]. Administration of clonidine, 0.2-0.8 mg/day, lowered supine PNE (p less than 0.01, p less than 0.02), and clonidine, 0.4-0.8 mg/day, lowered standing PNE (p less than 0.01, p less than 0.02). Maximal suppression of PNE occurred with 0.4 mg/day. Systolic blood pressure correlated with supine PNE (r = 0.055, p less than 0.05) at 0.2-0.8 mg/day clonidine, and standing PNE correlated (r = 0.72, p less than 0.01) at 0.2-0.6 mg/day. Plasma epinephrine concentration, plasma renin activity (PRA), and serum creatinine did not show any significant change. PRA did not correlate with blood pressure changes. Plasma clonidine concentration correlated reciprocally with the change in PNE (r = -0.59, p less than 0.01). These findings indicate that clonidine can return elevated PNE to normal levels in the vasodilator beta-blocker-treated patient and thus remove this abnormality as a contributing factor to pathogenetic mechanisms.

Adrenergic beta-Antagonists↗