Differences In Blood Pressure Responses Research Articles

Response of chronic renovascular hypertension to surgical correction or prolonged blockade of the renin-angiotensin system by two inhibitors in the rat.

1. Removal of the renal artery constriction but not of the clipped kidney restored the blood pressure to normal levels in Goldblatt two-kidney rats with hypertension of more than 4 months' duration. 2. Despite the differences in blood pressure response, both surgical procedures lowered plasma renin concentration to normal or below normal values. 3. Administration of the oral converting enzyme inhibitor SQ 14 225 produced a marked fall in blood pressure in Goldblatt kidney rats with chronic hypertension. However, a prolonged infusion of the angiotensin II antagonist saralasin was quite ineffective. The difference in response to the two inhibitors may have been due to bradykinin potentiation by the converting enzyme inhibitor. 4. Although plasma renin is often elevated in Goldblatt two-kidney rats with hypertension of more than 4 months' duration, the renin-angiotensin system plays no role in the maintenance of blood pressure at this stage.

Acebutolol in hypertension: Relationships between drug concentration and effects

Relationships between plasma concentrations of acebutolol (Ac) and its N-acetyl metabolite (Am) and pharmacological effects were studied in patients with essential hypertension. In an acute study (N=7) 400 mg oral acebutolol produced similar peak plasma levels of Ac and Am but Am had a longer half life. Group mean pulse and blood pressure fell significantly, although the size of individual blood pressure fall varied five-fold. There was no significant change in plasma renin activity. Correlations were found between drug concentration and β-blockade, assessed as % reduction in exercise tachycardia, and between both of these and the fall in post exercise systolic blood pressure. Similar comparisons were made in a chronic optimum dose study (N=11) both pre-dose and three hours post-dose. Am concentration was consistently higher than Ac at both times. Blood pressure was lowered equally pre-and post-dose when compared to placebo and plasma renin activity (PRA) was reduced on active treatment. Correlations were again shown between drug concentrations and β-blockade but none were found with changes in blood pressure or PRA. Between subject differences in blood pressure response could not be fully explained in terms of the other measurements but it is unlikely that pharmacokinetic differences are the major source of this variability.

Estimating renin participation in hypertension: Superiority of converting enzyme inhibitor over saralasin

This study was designed to examine more closely the differences in blood pressure responses in hypertensive patients to two agents which block the renin-angiotensin system. Accordingly, 39 seated patients received under the same conditions both saralasin, an octapeptide competitive antagonist of angiotensin II, and the nonapeptide converting enzyme inhibitor, SQ20881, which blocks the generation of angiotensin II from angiotensin I. A second component of the study involved administration of these agents in 10 additional studies in anephric subjects. Although both agents produced maximal responses in blood pressure that correlated well with each other (p < 0.001) and with the pretreatment plasma renin levels (p < 0.001), analysis of the results by renin subgroups revealed significant differences. Thus, both drugs lowered the diastolic pressures of patients with high renin levels, but converting enzyme inhibitor produced changes of greater amplitude (p < 0.05). In contrast, saralasin was consistently pressor in both patients with low renin levels and anephric patients in whom converting enzyme blockade produced no significant changes in blood pressure. Another impressive disparity in the responses to the two agents occurred in the group with normal renin levels in whom saralasin produced either neutral or pressor responses (mean change was +2.0 ± 1.5 standard error of the mean (SEM) per cent control diastolic pressure) whereas the converting enzyme inhibitor consistently induced depressor responses (mean change was −10.2 ± 1.2 per cent, p < 0.001). Altogether, the results suggest that converting enzyme inhibitor tests for angiotensin II-dependent blood pressure with more sensitivity than the partial agonist saralasin. Moreover, it is unlikely that the differences between the responses to the two agents were due to bradykinin accumulation, since depressor responses to converting enzyme inhibitor were not observed in the patients with low renin levels and the anephric patients.

Unexpected pressor responses to propranolol in essential hypertension: An interaction between renin, aldosterone and sympathetic activity

The blood pressure response to propranolol treatment was analyzed retrospectively in 187 patients with benign essential hypertension. In most patients (102 patients, 54 per cent) systolic and/ or diastolic blood pressure was decreased by more than 10 per cent (responders). No significant change in blood pressure occurred in 35 per cent (65 patients) of the patients (nonresponders). Surprisingly, in 20 patients (11 per cent) systolic (8 patients) and/or diastolic (14 patients) blood pressure was increased by more than 7 per cent (pressor-responders). All three subgroups received similar amounts of propranolol and irrespective of the effect on the blood pressure, propranolol produced a similar reduction in pulse rates, suggesting similar degree of beta blockade. The three subgroups did not differ in their clinical characteristics, except that the nonresponders were significantly older than the responders. Pretreatment renin values were highest in the responders, somewhat lower in the nonresponders and significantly lower in the pressor-responders. In a representative subset of 66 patients, control and treatment values for plasma renin activity and aldosterone excretion were compared. The responders had the most pronounced decreases in both renin and aldosterone. In striking contrast, no significant changes were observed in the two hormones in those patients whose blood pressure levels rose. Moreover, in the pressor-responders, the drug produced the greatest increases in body weight, reflecting sodium retention. The differences in blood pressure responses observed in different patients may be explained by various interplays between the drug-induced suppression of renin and aldosterone, and the operation of unopposed or reactive alpha sympathetic activity. The latter is presumably active in all patients tending to cause vasoconstriction and hence an increase in peripheral resistance. In the pressor-responders such unopposed alpha-tone combined with the demonstrated lack of renin and aldosterone suppression with attendent fluid retention could work to produce the paradoxical pressor responses. In contrast, in those whose blood pressure levels drop, the drug-induced suppression of renin leads to decreased peripheral resistance despite the unopposed alphatone. The accompanying decrease in aldosterone limits sodium retention and contributes to the fall in blood pressure levels.

Cardiopulmonary responses of male and female swine to simulated high altitude.

Cardiopulmonary responses of male and female swine to simulated high altitude.

Investigation of the Cardiovascular Response of the Dog to l-Phenyl-2-hydrazinopropane

Results of a further attempt to determine a basis for the qualitative difference in blood pressure response of the human and the dog to l-phenyl-2-hydrazinopropane are reported. Elimination of arterial pressure level as a factor influencing the circulatory response of the dog to this compound removes the last possibility for a circumstantial basis for the difference. Mechanism studies indicate that the canine pressor response is a neurotropic, sympathetic effect mediated, for the most part, as a direct action on myoneural junction receptor sites with a lesser component of indirect action on these sites related to MAO inhibition or the peripheral release of catecholamines from blood vessel walls. Evidence presented by certain clinical investigators points to either a ganglionic or an adrenergic block as responsible for the human antihypertensive effect.

Investigation of the Cardiovascular Response of the Dog to 1-Phenyl-2-hydrazinopropane

Results of an attempt to determine the basis for the qualitative difference in blood pressure response of the human and the dog to 1-phenyl-2-hydrazinopropane are reported. This difference is not attributable to anesthesia or to mode of administration of the compound, nor is it involved with the recording position of the individual. A possible explanation for the difference, which is involved with action mechanism, is provided.