Comparison of the anti-hypertensive response to beta-adrenoceptor blocking drugs in intact and adrenal-demedullated spontaneously hypertensive rats.

1 The beta-adrenoceptor blocking drugs atenolol, metoprolol, practolol, propranolol, timolol and oxrenolol (as racemates) were administered acutely at three dose levels (0.01, 0.03 and 0.1 mmol/kg i.p. or s.c.) to spontaneously hypertensive rats with intact adrenal glands (SH-rats) and following unilateral adrenalectomy and contralateral adrenal-demedullation (SHAD-rats). Changes in mean arterial pressure and heart rate were determined via an indwelling aortic catheter, with the animals placed in a quiet environment. 2 All drugs significantly lowered the blood pressure of SHAD-rats, and these responses were not always associated with changes in basal heart rate. 3 With the exception of metoprolol and atenolol, the beta-adrenoceptor blocking drugs were less effective as anti-hypertensives in SH- than in SHAD-rats. Notably, timolol and oxprenolol lowered the blood pressure of SH-rats at low doses only, whereas propranolol evoked a pressor response in this model. 4 Whilst (+)-propranolol lowered the blood pressure of SHAD-rats only at a dose which caused myocardial depression, the anti-hypertensive response to (--)-propranolol did not parallel changes in heart rate and was preceded by a pressor response. 5 The results imply that adrenal catecholamine release contributes towards masking the anti-hypertensive effects of some beta-adrenoceptor antagonists in SH-rats.     

Prednisolone-3,20-bisguanylhydrazone: binding in vitro to sodium-and-potassium-activated adenosine triphosphatase of guinea pig heart ventricular muscle.

Spontaneously hypertensive rats and normotensive Kyoto Wistar controls were divided into 3 groups of 10 animals each and treated with phenoxybenzamine (5 mg/kg once daily), propranolol (25 mg/kg twice daily) or saline (once daily). After 5 weeks the in vitro incorporation of D-[U-14C]-glucose into aortic lipids and glycogen was measured in the presence and absence of insulin (1 mU/ml). In both normotensive and hypertensive rats treated with propranolol 14C-incorporation into triglycerides was reduced. Furthermore, insulin significantly stimulated 14C-incorporation into triglycerides, phospholipids and glycogen in propranolol-treated hypertensive rats. This effect was not statistically significant (0.05 less than p less than 0.1) in propranolol-treated normotensives. Phenoxybenzamine treatment did not significantly modify aortic lipogenesis or glycogen synthesis from glucose. Chronic propranolol treatment of spontaneously hypertensive rats resulted in aortic tissue becoming sensitized to insulin. Possible mechanisms and explanations for this are discussed.     

Long-term treatment with nebivolol improves arterial reactivity and reduces ventricular hypertrophy in spontaneously hypertensive rats

The aim of this study was to assess the effects of long-term nebivolol therapy on high blood pressure, impaired endothelial function in aorta, and damage observed in heart and conductance arteries in spontaneously hypertensive rats (SHR). For this purpose, SHR were treated for 9 weeks with nebivolol (8 mg/kg per day). Untreated SHR and Wistar Kyoto rats were used as hypertensive and normotensive controls, respectively. The left ventricle/body weight ratio was used as an index of cardiac hypertrophy, and to evaluate vascular function, responses induced by potassium chloride, noradrenaline, acetylcholine, and sodium nitroprusside were tested on aortic rings. Aortic morphometry and fibrosis were determined in parallel by a quantitative technique. Systolic blood pressure, measured by the tail-cuff method, was lower in treated SHR than in the untreated group (194 +/- 3 versus 150 +/- 4 mm Hg). The cardiac hypertrophy index was significantly reduced by the treatment. In aortic rings, treatment with nebivolol significantly reduced the maximal response to both KCl and NA in SHR. In vessels precontracted with phenylephrine relaxant, activity due to acetylcholine was higher in normotensive rats than in SHR and the treatment significantly improved this response. The effect of sodium nitroprusside on aortic rings was similar in all groups. Medial thickness and collagen content were significantly reduced in comparison with SHR. In conclusion, the chronic antihypertensive effect of nebivolol in SHR was accompanied by an improvement in vascular structure and function and in the cardiac hypertrophy index.     

Effects of chronic chrysin treatment in spontaneously hypertensive rats

The effects of an oral daily dose (20 mg kg(-1)) of the flavonoid chrysin for 6 weeks in spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY) were analysed. Chrysin reduces SHR elevated blood pressure, cardiac hypertrophy and functional vascular changes, but is without effect in WKY. These protective effects were associated with a reduced oxidative status due to the antioxidant properties of the drug.     

Arterial reactivity, blood pressure, and plasma levels of atrial natriuretic peptides in normotensive and hypertensive rats: effects of acute and chronic administration of atriopeptin III

We compared acute and chronic effects of atriopeptin III in normotensive and spontaneously hypertensive rats. Atriopeptin III relaxed isolated aortae and intrarenal microarteries but not coronary and mesenteric microarteries of normotensive rats. Effects on arterial smooth muscle were comparable in hypertensive and normotensive rats and were not affected by long-term treatment of the animals with the peptide. Acute administration of atriopeptin III (4-400 nmol/kg, intravenously) reduced systolic blood pressure in conscious spontaneously hypertensive and renal hypertensive rats but not in normotensive rats. In spontaneously hypertensive rats, nephrectomy increased the sensitivity to and the duration of the acute antihypertensive effect. Renal subcellular fractions rapidly inactivated atriopeptin III in vitro. This atriopeptinase activity was comparable for normotensive and spontaneously hypertensive rats and was not affected by long-term treatment of the rats with the peptide. Continuous administration of low doses of atriopeptin III (0.4 and 4.0 nmol/kg/h, intravenously (i.v.) during 7 days) caused a progressive reduction in systolic blood pressure in spontaneously hypertensive but not in normotensive rats. It did not affect plasma levels of aldosterone or renin and resulted in less than a doubling of the plasma levels of atrial natriuretic peptides. These findings confirm that atrial natriuretic peptides preferentially relax the renal microvasculature. They demonstrate that although atriopeptin III comparably relaxes arterial smooth muscle of normotensive and spontaneously hypertensive rats, both acute and chronic administration of the peptide preferentially lower blood pressure in hypertensive rats. Rather than contributing to the effects on blood pressure, the kidneys modulate the duration of action of atrial natriuretic peptides.     

The effect of prostaglandin E2 on the arterial blood pressure of normotensive and spontaneously hypertensive rats

1 In anaesthetized rats, injection of prostaglandin E(2) (0.5-5.0 mug/kg i.v.) caused a dose-dependent vasodepressor response. The magnitude of response was significantly greater in spontaneously hypertensive rats than in normotensive rats.2 In spontaneously hypertensive rats, the magnitude of the prostaglandin-induced depressor response was closely correlated with blood pressure. The higher the blood pressure, the greater was the response evoked by prostaglandin.3 In spontaneously hypertensive rats, a combination of guanethidine plus hydralazine reduced both blood pressure and prostaglandin-induced depressor responses.4 Spontaneously hypertensive rats and normotensive rats did not differ in the magnitude of their vasodepressor responses to intravenously administered acetylcholine or isoprenaline.     

Antihypertensive activity of indolepyruvic acid: a keto analogue of tryptophan.

We studied the effect of indole-3-pyruvic acid (IPA) on systolic blood pressure of normotensive, spontaneously hypertensive, DOCA + salt hypertensive, and Grollman hypertensive rats. Experiments were also carried out in order to investigate whether IPA may influence the development of hypertension in spontaneously hypertensive rats. Age-matched normotensive, spontaneously hypertensive, DOCA + salt hypertensive, and Grollman hypertensive rats treated with N-methylglucamine, were used as controls. Acute oral (up to 50 mg/kg) and intravenous (5 mg/kg) administration of IPA did not change systolic blood pressure in any models of hypertension. By contrast, a repeated administration of IPA (100 mg/kg/day, by oral gavage for 10 days) significantly decreased systolic blood pressure in all models of hypertension, while it elicited no significant effect in normotensive rats. Moreover, when IPA was given daily to 5-week-old spontaneously hypertensive rats for 7 weeks, it partially inhibited the development of hypertension. In addition, chronic administration of IPA caused enhanced levels of tryptophan and 5-hydroxyindoleacetic acid in the cortex and diencephalon. Brainstem serotonin content in both normotensive and spontaneously hypertensive rats was also enhanced by IPA treatment. Our results suggest that IPA lowers blood pressure in different rat models of hypertension and this effect seems to be correlated with an increase in cerebral serotonin metabolism.     

Effects of medium-chain triglyceride (MCT) application to SHR on cardiac function, hypertrophy and expression of endothelin-1 mRNA and other genes

In spontaneously hypertensive rats a decrease occurs in myocardial energy supply from long-chain triglyceride (LCT) by CD36 gene mutation-induced dysfunction. We investigated whether long-term intake of medium-chain triglyceride, which enters into cells without CD36, upregulates fatty acid metabolic capacity in the heart of spontaneously hypertensive rats, and whether this upregulation improves cardiac hypertrophy and molecular markers. Male 4-week-old spontaneously hypertensive rats were given medium-chain triglyceride (SHR-MCT) or LCT (SHR-LCT) for 16 weeks. After hemodynamic measurement, we determined myocardial fatty acid metabolic enzyme activity and mRNA expression of molecular markers (endothelin-1, alpha-skeletal actin, angiotensin-converting enzyme and brain natriuretic peptide) for cardiac hypertrophy. We used Wistar-Kyoto rats (WKY-MCT and WKY-LCT) as controls. When compared with SHR-LCT rats, SHRMCT rats showed an increase in myocardial fatty acid metabolic enzyme activity and improvement in cardiac function (left ventricular end-diastolic pressure and +dP/dt/P) and cardiac hypertrophy. Blood pressure did not differ between them. The mRNA expression of endothelin-1, alpha-skeletal actin, angiotensin-converting enzyme and brain natriuretic peptide in the heart was significantly higher in SHR-LCT than in WKY-MCT and WKYLCT rats, and there was no significant difference between SHRLCT and SHR-MCT. These findings suggest that medium-chain triglyceride application to spontaneously hypertensive rats improves decreased cardiac function and cardiac hypertrophy without affecting blood pressure and myocardial mRNA expression of molecular markers. Because mechanical stress to the heart is similar between SHR-LCT and SHR-MCT, this may be a reason for the lack of difference in expression of molecular markers.     

Triglyceride-lowering effect of pitavastatin [corrected] in a rat model of postprandial lipemia

We examined the effects of gamma-aminobutyric acid (GABA) on the blood pressure in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. A single oral administration (0.5 mg/kg) significantly lowered the systolic blood pressure in spontaneously hypertensive rats, but not in normotensive rats. In the mesenteric arterial bed, the perivascular nerve stimulation-induced increase in perfusion pressure and noradrenaline release were significantly inhibited by GABA in spontaneously hypertensive rats, but not in normotensive rats, and attenuated by the selective GABA(B) receptor agonist, baclofen, but not by the selective GABA(A) receptor agonist muscimol. The inhibitory effects of GABA on the perivascular nerve stimulation-induced increase in perfusion pressure and noradrenaline release were completely antagonized by the selective GABA(B) receptor antagonist, saclofen, but not by the selective GABA(A) receptor antagonist, bicuculline. These results suggest that, in spontaneously hypertensive rats, GABA has an antihypertensive effect due to its inhibition of noradrenaline release from sympathetic nerves in the mesenteric arterial bed via presynaptic GABA(B) receptors.     

Effects of beta-adrenergic receptor blocking agents on blood pressure in conscious hypertensive rats.

The effects of beta-adrenergic receptor blocking agents administered i.v. on the blood pressure in conscious spontaneously hypertensive rats (SHR), renal hypertensive rats (RHR) and normotensive Wistar strain rats (NR) were studied. dl-Propranolol and dl-YB-2, 1 mg/kg i.v., caused a sustained rise in blood pressure in SHR and RHR. The maximum response of each beta-blocking agent after phentolamine, 10 mg/kg i.v., in SHR and RHR was significantly larger than that in NR. The potency ratio for the hypertensive activities of the 1- and d-isomers of propranolol and YB-2 was similar to the ratio of their beta-blocking activities. The pressor effects of the beta-blocking agents after phentolamine were significantly inhibited by adrenalectomy, reserpinization and pretreatment with hexamethonium. The results suggest that the pressor effect of the beta-blocking agents may be due to their beta-blocking activities and the unmasking of alpha-receptor activities of the blood vessels. Furthermore, the greater pressor effect of the agents observed in hypertensive rats is attributed to a greater activity of the sympathetic nervous system in these rats as compared to normotensive rats.     

Lysine incorporation in vessels of spontaneously hypertensive rats: effects of adrenergic drugs

Synthesis of vascular proteins was investigated by measurement of the incorporation of ³H-lysine into the protein fractions in arteries in young normotensive or genetically hypertensive rats. The effect of 14 days of antihypertensive therapy with clonidine, propranolol, and phenoxybenzamine was examined. The rate of incorporation of ³H-lysine into the non-collagen protein in internal spermatic and testicular arteries or mesenteric arteries in 8-week old spontaneously hypertensive rats/NIH (SHR/N) and in stroke-prone spontaneously hypertensive rats/NIH (SHR SP/N) was significantly greater than that of Wistar Kyoto rats/NIH (WK/N). S.c. injection of clonidine, 200 μg/kg twice daily decreased the incorporation of tritiated lysine into the non-collagen protein in internal spermatic arteries in each strain and mesenteric arteries in WK/N and SHR SP/N, concomitant with a reduction of development of blood pressure. Similar results were obtained following phenoxybenzamine treatment (3.5 mg/kg s.c. twice daily) and to a lesser extent, following smaller dose of same drug (1 mg/kg s.c. twice daily). Propranolol administration, 3 mg/kg s.c. twice daily, was ineffective in decreasing non-collagen protein synthesis in these small arteries and failed to reduce the blood pressure in any strain. The incorporation rates of tritiated lysine into the collagen and elastin were similar in the examined vessels in each strain treated with saline. Decreased collagen synthesis was observed following clonidine treatment in internal spermatic and testicular arteries in each strain. Other vascular proteins did not change despite the effective antihypertensive treatment. A high incidence of muscular hypertrophy of the media in internal spermatic arteries in SHR/N or SHR SP/N was observed in non-treated and propranolol-treated animals. This hypertrophy was not seen following clonidine or high doses of phenoxybenzamine. These results indicate that increased non-collagen protein synthesis in the small arteries in young genetically hypertensive rats precedes the development of severe hypertensive vascular lesions and may be involved in the pathogenesis of spontaneous hypertension.     

Effects of single and repeated oral administration of MK-421 and captopril on blood pressures in normotensive and experimental hypertensive rats

In the single dose study, the aortic blood pressure in conscious normotensive rats, 2-kidney, 1-clip renal hypertensive rats (2K-RHR), 1-kidney, 1-clip renal hypertensive rats (1K-RHR) or DOCA hypertensive rats was measured for 24 hr after the oral administration of angiotensin converting enzyme (ACE) inhibitors such as MK-421 or captopril. MK-421 at 3 mg/kg and captopril at 10 mg/kg markedly lowered the blood pressure of 2K-RHR. MK-421 at 10 mg/kg and captopril at 30 mg/kg only modestly lowered the blood pressure of 1K-RHR. In contrast, both ACE inhibitors failed to reduce blood pressure in DOCA and normotensive rats. In the repeated dose study, the systolic blood pressures in normotensive rats, 2K-RHR or spontaneously hypertensive rats (SHR) were measured twice a week for 3 weeks treatment of either MK-421 at 3 mg/kg or captopril at 10 mg/kg. Both ACE inhibitors produced significant antihypertensive effects in these model rats, and the effects were sustained throughout the treatment period. The antihypertensive effects in 2K-RHR were greater than those in SHR and normotensive rats. These results indicate that MK-421 and captopril cause the most significant antihypertensive effect in 2K-RHR in which the renin-angiotensin system played a dominant role in blood pressure regulation. The antihypertensive effect of MK-421 was approximately 3 times as potent as that of captopril in these hypertensive models.     

Hypotensive effects of diltiazem hydrochloride in the normotensive, spontaneously hypertensive and renal hypertensive rats (author's transl)

In conscious and anesthetized normotensive rats, intravenous administration of diltiazem (0.1--3 mg/kg) produced a dose-related decrease in blood pressure. Administration of diltiazem (1--50 mg/kg) into the duodenum of anesthetized rats also reduced the blood pressure in a dose related manner. In parallel with the change in blood pressure, the heart rate increased in conscious rats and decreased in anesthetized animals. Such an increase in the heart rate was suppressed by pretreatment with propranolol. Similarly, in conscious spontaneously hypertensive rats (SHR), diltiazem dose-dependently decreased the blood pressure and increased the heart rate after intravenous administration (0.03--1 mg/kg). Oral administration of diltiazem (100 mg/kg) also reduced the blood pressure of SHR. In addition, the progressive increase in blood pressure in young SHR was significantly suppressed by chronic oral administration of diltiazem (30 mg/kg). The blood pressure in conscious renal hypertensive rats was also decreased with diltiazem (50 mg/kg p.o.). On the other hand, it was demonstrated that the pressor responses to norepinephrine and angiotensin II in the anesthetized normotensive rats were non-competitively inhibited by intravenous administration of diltiazem at a dose which had no effect on the blood pressure.     

Antihypertensive effect of CV-4093.2HCl, a new calcium antagonist, in three rat models of hypertension

The hypotensive action of CV-4093.2HCl (CV-4093), a new calcium antagonist, was studied in spontaneously hypertensive, renal hypertensive, DOCA-salt hypertensive and normotensive rats. CV-4093 (3 and 10 mg/kg, p.o.) dose-dependently decreased systolic blood pressure in the three types of hypertensive rats. At the dose of 10 mg/kg, the compound decreased the blood pressure to the normotensive level between 1 and 3 hr after it was administered; the antihypertensive effect lasted for at least 8 hr. The systolic blood pressure in normotensive rats was also decreased at 3 and 10 mg/kg, p.o., but less evidently than in the hypertensive rats. When the antihypertensive effect of CV-4093 was compared with that of seven known calcium antagonists in spontaneously hypertensive rats, it was the most potent and the most long-lasting.     

Alterations in blood pressure of normotensive and hypertensive rats following intrathecal injections of neuropeptide Y

The effect of the intrathecal administration of neuropeptide Y (NPY) on blood pressure and heart rate of anesthetized normotensive and hypertensive rats was studied. Neuropeptide Y was observed to produce a decrease in the blood pressure of Sprague-Dawley, Wistar Kyoto (WKY), DOCA-salt, and DOCA-sham control rats. The maximum percent decrease in blood pressure of Sprague-Dawley rats was 12.8 and 15.2% in response to 0.1 and 1.0 nmol NPY, respectively. Similar changes in heart rate were observed. The depressor effect of intrathecal NPY was attenuated by prior treatment with yohimbine and propranolol but not prazosin. The depressor effect of intrathecal NPY observed in normotensive and DOCA-salt hypertensive rats was not seen in the spontaneously hypertensive rat (SHR). The studies extend to the spinal cord the list of regions and tissues where NPY can produce physiological effects. It is concluded that the effects of NPY are closely associated with sympathetic preganglionic neurons in the spinal cord that the depressor effect of NPY involves alpha 2 and beta adrenoceptors, and that a loss of the depressor effect of NPY may contribute to the development or maintenance of hypertension in the SHR.     

Effect of acebutolol, a cardioselective beta-adrenoceptor blocking agent, on the blood pressure in rats (author's transl)]

The effects of acebutolol, a cardioselective beta-adrenoceptor blocking agent, on the systolic blood pressure and heart rate were investigated in conscious Kyoto Wistar normotensive rats (WKY), spontaneously hypertensive rats (SHR) and DOCA-NaCl hypertensive rats (DOCA rats) and the results compared with those of propranolol and practolol. In WKY and DOCA rats, the intraperitoneal administration of acebutolol, propranolol and practolol (0.5 approximately 20 mg/kg) produced a hypotensive action, however, these effects were observed only with restricted doses and there was no evidence of a dose-dependency. The heart rate was decreased by acebutolol and propranolol, but was increased by practolol which possesses an intrinsic sympathomimetic activity. In SHR, propranolol produced a dual action, a slight rise followed by a slight fall, the change not being significant, while practolol induced a slight hypertension. On the other hand, acebutolol in high doses induced a dose-dependent hypotensive action. The heart rate was markedly and dose-dependently decreased by these three agents. Thus, while propranolol and practolol produced hypotensive effects in WKY and DOCA rats, acebutolol produced hypotensive effects in WKY, SHR and DOCA rats. These results suggest that acebutolol is a beta-adrenoceptor blocking agent which possesses hypotensive activity in hypertensive rats.     

The effects of chronic lead treatment and hypertension on the severity of cardiac arrhythmias induced by coronary artery occlusion or by noradrenaline in anaesthetised rats

The aim of this study was to investigate whether chronic (3 months) lead (250 or l000ppm), administered as lead acetate in the drinking water, commencing either after weaning (in normotensive or spontaneously hypertensive male rats) or from conception (normotensive rats only) altered the susceptibility of the heart to arrhythmias induced either by coronary artery occlusion or by noradrenaline. Treatment with lead alone had no marked effect on the arrhythmias elicited by either method. Spontaneously hypertensive rats treated with either dose of lead exhibited more ectopic beats following coronary artery occlusion than normotensive rats but not more than those observed in control spontaneously hypertensive rats. An enhanced arrhythmogenic effect of noradrenaline was observed only in hypertensive rats administered 250 ppm lead. Both doses of lead accelerated the development of high blood pressure and in normotensive rats the higher dose also resulted in an elevated pressure. Following administration of lead, blood lead concentrations were elevated to 0.96 and 2.11 mol 1^–1 after 250 and 1000 ppm, respectively. Accumulation of lead in heart and bone was also observed. We conclude that chronic exposure to these concentrations of lead, when combined with high blood pressure, slightly enhances the susceptibility of the heart to arrhythmias induced by myocardial ischaemia.     

Effect of inhibition of nitric oxide synthesis on the uptake of LDL and fibrinogen by arterial walls and other organs of the rat.

1. The effects of administering 3 mg ml-1 NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO), on the uptake of low density lipoprotein (LDL), fibrinogen and blood pressure were determined in conscious, unrestrained, cannulated normotensive and spontaneously hypertensive (SHR) Wistar rats. 2. The uptake of LDL and fibrinogen, labelled respectively with 125I or 131I via the adduct tyramine cellobiose ([125I]TC-LDL and [131I]TC-fibrinogen), were compared in aortic walls, heart, skeletal muscle, lung, liver, kidney and adrenal during the final 24 h of 6 days' administration of L-NAME in the drinking water. 3. In control normotensive rats, the systolic blood pressure did not change significantly over 6 days, while administration of L-NAME in normotensive rats increased the blood pressure progressively and significantly to about 170 mmHg over the same period. 4. In normotensive rats L-NAME increased significantly the uptake of both LDL and fibrinogen by aortic walls and heart, but not by muscle, lung, liver, kidney and adrenal. 5. The blood pressure in SHR was about 170 mmHg before administration of L-NAME and did not increase significantly after 6 days of treatment. In these rats the uptake of LDL or of fibrinogen was increased only in the heart but not in aortic walls nor in any of the other organs.(ABSTRACT TRUNCATED AT 250 WORDS)     

长期服用一种自由基清除剂ONO—3144对易卒中自发高血压大鼠的影响

AIM:To clarify the preventive effects of ONO-3144, a free radical scavenger, on stroke-prone spontaneously hypertensive rats (SHRSP) and free radicals related to the hypertensive disorders. METHODS: Drugs with powdered chow were administered orally to the rats from 2- to 14-month-old. Body weight, blood pressure, rectal temperature, oxygen consumption rate, thyroid hormones, lipids, platelet number, ocular fundus, autopsy, and life span were investigated. RESULTS: ONO-3144 did not affect the growth, blood pressure, concentrations of thyroid hormones and lipids in the blood, but decreased the rectal temperature and oxygen consumption rate. ONO-3144 also prevented the platelet number decrease, sclerotic change of retinal artery, edematous and hypertrophic changes in parenchymal and circulatory organs. Both the average life-span and the longest life time of SHRSP given 40 mg/kg ONO-3144 were longer than those of normotensive rats and no administration hypertensive rats. CONCLUSION: The oxidative free radic     

Raynaud's phenomenon as side effect of beta-blockers in hypertension.

A series of 102 hypertensive patients were assessed for the frequency of symptoms of Raynaud's phenomenon and absent peripheral pulses. Out of 21 patients receiving methyldopa alone only one had cold hands and feet whereas among patients on beta-blockers the incidence was 50%. The frequency of both symptoms and absent pulses was highest in patients taking propranolol compared with those taking atenolol or oxprenolol. Patients without a foot pulse were much more likely to have cold hands. A change from propranolol to oxprenolol in some symptomatic patients resulted in improvement. In two patients the skin temperature fell after an 80-mg dose of propranolol. The mechanism by which beta-blockers induce Raynaud's phenomenon is still not clear.