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Biomedical subjects

S Julius

Publications and source records attributed to S Julius.

At least 199 records · Page 11Linked to original sources
PubMed1976

Dissociation of the renin lowering and antihypertensive actions of propranolol.

Suppression of renin release by beta-adrenoceptor blocking drugs has been advocated as the prime blood pressure lowering mechanism of these agents. The present report casts doubt on this proposition in three ways. In the first study, involving 22 patients with borderline hypertension, patients with elevated plasma renin levels showed normalization of the blood pressure after pharmacological autonomic blockade with intravenous atropine, propranolol and phentolamine, the time course of the pressure fall being such as to exclude suppression of renin release as the antihypertensive mechanism. It is clear that in patients with mild hypertension and high plasma renin levels, the elevation of blood pressure is maintained by a neurogenic mechanism, the elevated plasma renin having no direct role in sustaining the higher blood pressure. In two additional studies involving 21 patients in all with mild to moderately severe essential hypertension, to whom propranolol was administereed by mouth for 1--3 months, two findings were of interest:1) patients with low-renin essential hypertension showed a good antihypertensive response to propranolol, and 2) in some patients a dosedependent dissociation of the renin and blood pressure lowering action of propranolol could be demonstrated. These findings militate against the assumption that propranolol selectively lowers the blood pressure in "renin-dependent" hypertension, and strongly suggest that the antihypertensive action of this drug is not mediated by depression of plasma renin activity.

Atropine↗
PubMed1975

Autonomic nervous cardiovascular regulation in borderline hypertension.

Borderline hypertension attracts investigative interest since it is an early predictor of established hypertension and its sequelae. This condition offers the opportunity of studying arterial hypertension at its inception, before the development of secondary pressure-related changes. A number of abnormalities of the circulation have been described in borderline hypertension. The peripheral resistance is either elevated or inappropriately adjusted to the prevailing increased cardiac output and blood flow. Cardiac output, heart rate and stroke volume are elevated in a proportion of patients. Decreased plasma volume, enhanced pressor responsiveness and elevated plasma renin activity have also been noted. All these changes could hypothetically be explained by a neurogenic mechanism. Although the experimental evidence supporting a neurogenic origin of borderline hypertension is incomplete and often indirect, most findings point toward an abnormal autonomic control of the circulation in this disorder. It is postulated that in a subgroup of patients with borderline hypertension a neurogenic mechanism is in fact operative. There is a need for further characterization of this category of borderline hypertension and for description of its natural history, particularly in relation to the possible subsequent development of essential hypertension.

Autonomic Nervous System↗
PubMed1975

Relation of renin status to neurogenic vascular resistance in borderline hypertension.

The relation of renin-angiotensin status to general hemodynamics and to neurogenic vascular resistance was studied in patients with border-line hypertension. Plasma renin activity during standing was referred to a standard renin-urinary sodium nomogram derived from 18 normal subjects. Among 22 patients with borderline hypertension the renin level was high in 8, low in 4 and within normal limits in the remaining 10. In patients with borderline hypertension and high or normal levels of plasma renin activity, the blood pressure elevation was due to increased total peripheral vascular resistance. In contrast, in patients with low renin borderline hypertension, total peripheral resistance was not significantly elevated; the blood pressure elevation reflected a cardiac index 12 percent higher than that in normal subjects. The neurogenic contribution to total peripheral vascular resistance was assessed by studying the effects of alpha adrenergic blockade with phentolamine, after prior autonomic blockade of the heart with atropine (0.04 mg/kg body weight) and propranolol (0.2 mg/kg). Phentolamine (15 mg) produced an immediate reduction in total peripheral resistance of 12.0 +/- 6.7 percent in patients with high renin borderline hypertension (P less than 0.01) but no change in normal subjects or those with borderline hypertension and normal or low renin levels. Normalization of the blood pressure followed "total" autonomic blockade with atropine, propranolol or phentolamine only in patients with high renin borderline hypertension. It is concluded from these preliminary data that in high renin borderline hypertension the blood pressure elevation is sustained by neurogenic mechanisms. The elevated renin level in these patients is probably an expression of increased sympathetic nervous activity. Although the elevated plasma renin level may possibly be contributing to the generation of higher sympathetic tone, or data do not support a direct role of circulating angiotensin in the maintenance of the elevated vascular resistance.

Adolescent↗
PubMed1975

Role of the autonomic nervous system in mild human hypertension.

1. Some of the haemodynamic abnormalities in mild (borderline) human hypertension appear to be neurogenic, since they can be completely abolished by pharmacological autonomic blockade. 2. The cardiac output is elevated in 30% of patients through increased sympathetic drive and decreased parasympathetic inhibition. 3. In the remainder, the higher blood pressure is maintained by increased total peripheral vascular resistance. 4. In approximately 30% of this latter group, the higher vascular resistance is maintained solely by increased alpha-adrenergic tone. 5. Elevated plasma renin activities in a proportion of cases are probably due to generalized increase in sympathetic nervous activity. 6. Patients with mild hypertension thus show increased sympathetic drive to the heart and arterioles as well as decreased cardiac parasympathetic inhibition. It is presumed that the increased plasma renin is also neurogenic. 7. Such a widespread distribution of altered autonomic tone suggests aberration of the function of the integrative centres of cardiovascular control. 8. Evidence is presented of a possible psychosomatic origin of these changes in some cases.

Adolescent↗
PubMed1975

Arterial pressure, cardiac output and systemic resistance before and after pithing in normotensive and spontaneously hypertensive rats.

After complete cardiovascular denervation mean arterial pressure (MAP) falls to almost equally low levels in spontaneously hypertensive rats (SHR) and normotensive control rats (NCR). This has earlier been suggested to indicate a dominance of neurogenic mechanisms in established SHR hypertension. -- In the present study, total peripheral resistance (TPR) remains, however, some 35 per cent higher in adult SHR than in NCR after pithing while cardiac output (CO), and stroke volume, is 35 per cent lower in SHR. These opposite differences in TPR and CO after denervation, resulting in equal MAP levels in SHR and NCR, seem rather to be a consequence of the rapidly established structural adaptation that affects all SHR high-pressure cardiovascular sections. Thus, the SHR precapillary resistance vessels display thickened walls and luminal narrowing, which keeps TPR higher than in NCR even during maximal vasodilatation. Due to hypertrophy, the SHR left ventricle exhibits a reduced myocardial stretch for a given filling pressure and stroke volume is consequently reduced more than in NCR after complete denervation. -- Paradoxically, therefore, rather than reflecting any dominance of neurogenic mechanisms in established SHR hypertension the MAP equalization in SHR and NCR after cardiovascular denervation emphasizes the hemodynamic importance of cardiovascular structural changes present in hypertension.

Animals↗
PubMed1975

Altered cardiac responsiveness and regulation in the normal cardiac output type of borderline hypertension.

Of 145 patients with borderline hypertension, 30% had increased resting cardiac index (QI), whereas the remainder had normal values. The specific aim of this study was to investigate cardiac regulation in patients who had normal resting QI. Eighty-five control subjects were used for comparison. At rest, patients with normal QI showed evidence of decreased parasympathetic inhibition; the QI after injection of atropine increased less than in control subjects. After complete cardiac autonomic blockade with propranolol and atropine, QI and stroke volume were significantly lower in patients than in control subjects. The mechanism of this low QI was further analyzed. Central blood volume, which strongly correlates with stroke volume, was used as an estimate of the cardiac venous filling. After blockade, stroke volume was decreased in patients, but central blood volume was normal. Patients also showed a decreased heart rate and QI response to infusion of isoproterenol. It is therefore postulated that two components may be responsible for the low QI in the "denervated" heart: patients exhibit a decreased responsiveness to sympathetic stimulation, and they may also be less responsive to venous filling. Behind the facade of cardiac normality in these borderline hypertensive patients with normal cardiac output, there is evidence of altered autonomic control of the heart (decreased vagal inhibition) and of changed cardiac response to sympathetic stimulation and possibly to venous filling.

Adult↗