Gradual Increase In Blood Pressure Research Articles

Pathogenetic characteristics of the hormonal profile in rats subjected to restraint stress of different duration

The aim of the work is to ascertain the character of changes in the hormonal profile (concentrations of corticosterone, insulin, and adrenocorticotropic hormone) in conjunction with metabolic alterations and elevated blood pressure, which are induced in rats by restraint stress at 6th, 15th and 21st weeks of environmental space restriction.
 Materials and methods. A total of 55 normotensive male Wistar rats, aged 6–10 months, were assigned into 4 experimental groups (1 – intact control (10 rats); 2, 3 and 4 (15 rats each exposed to restricted space allowance)). All the animals were subjected to blood pressure (BP), blood glucose level and body weight measurements twice: at the stage of forming groups and at the 6th, 15th and 21st weeks. Plasma hormone concentrations (insulin, corticosterone, and ACTH) were examined by the immunoenzymatic method using commercial kits (Monobind, USA).
 Results. The body weight of the animals was significantly reduced by 20.72 % after 6 weeks of space allowance restriction, it was restored to baselines by the 15th week and exceeded control values by 26.1 % at the 21st week. BP levels showed an increasing trend, a dynamic increase in systolic pressure by 7 %, 17 % and 26 % was detected, respectively, as well as diastolic from the 15th week to the 21st week by 21.4 % and 37.0 %, respectively. Glucose concentration was within the euglycemic range. Changes in the hormonal profile showed an increase in the concentration of ACTH by more than 50 % and a decrease in insulin – by 34 % at the 6th week with a subsequent twofold decrease in the insulin concentration (at week 15) and a further more than twofold increase in ACTH at the 21st week. As for changes in the concentration of corticosterone, a peak increase of 3.77 times was noticed at the 15th week, followed by a decrease and restoration to the normative values by the 21st week.
 Conclusions. Even minor and unremarkable continuously acting stressors, which cannot be coped, become important triggers for hormonal profile and carbohydrate metabolism alterations as well as for a persistent increase in blood pressure, which manifest first by hypoinsulinemia, an increase in the level of ACTH, and a constant concentration of corticosterone. Long-term stress exposure contributes to a transient “peak” increase in the corticosterone level, a significant increase in insulin and a sustained increase in ACTH. Multidirectional changes in the levels of the studied hormones occur amidst a gradual increase in blood pressure and a stable increase in the level of glycemia.

Salt-loading promotes extracellular ATP release mediated by glial cells in the hypothalamic paraventricular nucleus of rats

Previously, we have shown that purinergic signalling is involved in the control of hyperosmotic-induced sympathoexcitation at the level of the PVN, via activation of P2X receptors. However, the source(s) of ATP that drives osmotically-induced increases in sympathetic outflow remained undetermined. Here, we tested the two competing hypotheses that either (1) higher extracellular ATP in PVN during salt loading (SL) is a result of a failure of ectonucleotidases to metabolize ATP; and/or (2) SL can stimulate PVN astrocytes to release ATP. Rats were salt loaded with a 2 % NaCl solution replacing drinking water up to 4 days, an experimental model known to cause a gradual increase in blood pressure and plasma osmolarity. Immunohistochemical assessment of glial-fibrillary acidic protein (GFAP) revealed increased glial cell reactivity in the PVN of rats after 4 days of high salt exposure. ATP and adenosine release measurements via biosensors in hypothalamic slices showed that baseline ATP release was increased 17-fold in the PVN while adenosine remained unchanged. Disruption of Ca2+-dependent vesicular release mechanisms in PVN astrocytes by virally-driven expression of a dominant-negative SNARE protein decreased the release of ATP. The activity of ectonucleotidases quantified in vitro by production of adenosine from ATP was increased in SL group. Our results showed that SL stimulates the release of ATP in the PVN, at least in part, from glial cells by a vesicle-mediated route and likely contributes to the neural control of circulation during osmotic challenges.

Association of Early Adulthood 25-Year Blood Pressure Trajectories With Cerebral Lesions and Brain Structure in Midlife

Midlife elevated blood pressure (BP) is an important risk factor associated with brain structure and function. Little is known about trajectories of BP that modulate this risk. To identify BP trajectory patterns from young adulthood to midlife that are associated with brain structure in midlife. This cohort study used data of US adults from Coronary Artery Risk Development in Young Adults (CARDIA), a prospective longitudinal study of Black and White men and women (baseline age 18 to 30 years) examined up to 8 times over 30 years (1985-1986 to 2015-2016). There were 885 participants who underwent brain magnetic resonance imaging (MRI) in the 25th or 30th year examinations. Analyses were conducted November 2019 to December 2020. Using group-based trajectory modeling, 5 25-year BP trajectories for 3 BP traits were identified in the total CARDIA cohort of participants with 3 or more BP measures, which were then applied to analyses of the subset of 853 participants in the Brain MRI substudy. Mean arterial pressure (MAP) was examined as an integrative measure of systolic and diastolic BP. With linear regression, the associations of the BP trajectories with brain structures were examined, adjusting sequentially for demographics, cardiovascular risk factors, and antihypertensive medication use. Brain MRI outcomes include total brain, total gray matter, normal-looking and abnormal white matter volumes, gray matter cerebral blood flow, and white matter fractional anisotropy. Brain MRI analyses were conducted on 853 participants (mean [SD] age, 50.3 [3.6] years; 399 [46.8%] men; 354 [41.5%] Black and 499 [58.5%] White individuals). The MAP trajectory distribution was 187 individuals (21.1%) with low-stable, 385 (43.5%) with moderate-gradual, 71 (8.0%) with moderate-increasing, 204 (23.1%) with elevated-stable, and 38 (4.3%) with elevated-increasing. Compared with the MAP low-stable trajectory group, individuals in the moderate-increasing and elevated-increasing groups were more likely to have higher abnormal white matter volume (moderate: β, 0.52; 95% CI, 0.23 to 0.82; elevated: β, 0.57; 95% CI, 0.19 to 0.95). Those in the MAP elevated-increasing group had lower gray matter cerebral blood flow (β, -0.42; 95% CI, -0.79 to -0.05) after adjusting for sociodemographics and cardiovascular risk factors. After adjustment for antihypertensive medication use, the difference was consistent for abnormal white matter volume, but results were no longer significant for gray matter cerebral blood flow. Among young adults with moderate to high levels of BP, a gradual increase in BP to middle-age may increase the risk in diffuse small vessel disease and lower brain perfusion.

A Case of Carney Triad Complicated by Renal Cell Carcinoma and a Germline SDHA Pathogenic Variant

Background: Carney triad is a rare multiple-neoplasia syndrome presenting as an association of paragangliomas (PGL), gastrointestinal stromal tumors (GIST), and pulmonary chondromas (CHO). Succinate dehydrogenase deficiency has been associated with several neoplasias, including Carney triad, renal cell carcinoma (RCC) and those associated with hereditary PGL/ pheochromocytoma (PHEO) syndromes. Clinical Case: A 57-year-old male diagnosed with hypertension at age 49, presented with a gradual increase in blood pressure over a period of 12 months. For seven years following his diagnosis of hypertension, the patient experienced episodic increases in blood pressure, to a systolic pressure greater than 180 mmHg associated with a tight band sensation around his forehead lasting half a day. Abdominal computed tomography (CT) revealed a left adrenal adenoma, a 5.1 cm para-aortic mass, and a right renal superior pole lesion measuring 2.5 cm, which was suspicious for a carcinoma. 123I-metaiodobenzylguanidine (123I-MIBG) and 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) scans were performed, which suggested the para-aortic mass to be consistent with a PGL. Additionally, 18F-FDG uptake was noted in the gastroesophageal region and was suspicious for a GIST. The left adrenal mass was not associated with 123I-MIBG or 18F-FDG activity. Chest CT demonstrated a right middle lobe lung lesion suggestive of a CHO, although no biopsy was performed. A diagnosis of Carney triad was made. The patient underwent surgical resection of the PGL and GIST, as well as a partial right nephrectomy. The PGL and GIST were positive for SDHA and negative for SDHB by immunohistochemical (IHC) staining. Pathology from the renal lesion was consistent with a 2.3 cm conventional clear cell renal carcinoma, with positive staining for SDHA and SDHB by IHC. The patient was found to harbor a germline heterozygous pathogenic variant (c.91 C>T, p.R31X) in SDHA which has been previously reported and results in loss of function of SDHA. SHDC hypermethylation was not detected in the PGL, GIST, or RCC. Additionally, DNA sequencing of the RCC did not indicate loss of heterozygosity at the variant region of interest. Although the SDHA disease-causing variant is responsible for the patients Carney triad phenotype, it is unclear if this variant is causative of the RCC. Conclusion: This is a novel presentation of a germline inactivating SDHA pathogenic variant in a patient with Carney triad complicated by RCC. However, an SDHA disease-causing variant was previously reported in a patient with comorbid GIST and RCC. This case provides further support to the increasing evidence that SDHx pathogenic variants may predispose patients to develop renal neoplasms.

Genetically determined hypertensive phenotype affects gut microbiota composition, but not vice versa

Research suggests reciprocal crosstalk between the host and gut bacteria. This study evaluated the interaction between gut microbiota and arterial blood pressure (BP) in rats. Continuous telemetry recordings of BP were started in 7-week-old normotensive Wistar--Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Two weeks later, half of the WKY and SHR were subjected to cross-transplantation of fecal matter, with stools harvested from either WKY or SHR and BP measurements until the age of 14 weeks. The composition of gut bacteria was assessed through analysis of the bacterial 16S ribosomal RNA gene sequence. The concentration of microbiota-derived metabolites was evaluated using HPLC-MS. There was a significant difference between WKY and SHR in the composition of gut bacteria at the start and end of the study. This was accompanied by significant histological differences in the colon. SHR, but not WKY, showed a gradual increase in BP throughout the experiment. For both WKY and SHR, there was no significant difference in BP or metabolic parameters between animals receiving fecal transplantation from either SHR or WKY. Genetically induced hypertension in SHR is associated with alterations in the composition of gut bacteria and histological morphology of the colon. An inter-strain fecal transplant does not affect BP and does not produce long-term changes in gut bacteria composition. We propose that the impact of the host genotype and/or phenotype on the gut bacteria may be greater than the impact of the gut bacteria on the host BP.

Ivabradine Use in Heart Failure After Myocardial Infarction Can Help with the Titration of the Dose of ARB/ACEI or β-Blockers: A Case Report

Introductionβ-blockers and angiotensin receptor blocker (ARB)/angiotensin-converting enzyme inhibitors (ACEI) are well known as critical therapies for improving the prognosis in patients with acute myocardial infarction, however, their use in some case may be limited. We believe that in such cases as when β-blockers and ARB/ACEI use is limited, ivabradine plays a potential role in the improvement of individual prognoses.Case PresentationA 49-year-old man from Dalian, China. He was diagnosed with acute inferior myocardial infarction in Feb, 2016. And he still experienced palpitations and heart failure after drug treatment and percutaneous coronary intervention (PCI). We used metoprolol at a low dose, although the symptoms were not relieved, β-blockers could not be used or increase dose because of his hypotension. Finally, we chose ivabradine to alleviate the symptoms of the patient related to heart rate and palpitations without affecting blood pressure so as to promote the recovery of heart function. We witnessed a gradual reduction in heart rate (HR) and a gradual increase in blood pressure. Finally, we administered an ARB and increased via titration the dose of ARB and β-blocker.ConclusionsWhen there are limitations to the use of ARB/ACEI and β-blockers, we can use ivabradine, which reduces HR without affecting blood pressure. Ivabradine can help with the titration of the dose of ARB/ACEI or β-blockers.

Abstract P441: Accelerated Age-dependent Cardiovascular and Cognitive Decline in Dahl-S Rats is Associated with Elevated Levels of an Endogenous Na/K-ATPase Inhibitor

Age-associated central arterial stiffening contributes to both cerebral arterial fibrosis and to cognitive impairment. Accelerated aging, accompanied by a gradual increase in blood pressure (BP) and aortic remodeling, occurs in Dahl-S rats (DSS) vs. normotensive Sprague-Dawley rats (S-D) counterparts even in the absence of a high salt intake. A novel pro-hypertensive factor marinobufagenin (MBG) is implicated in DSS hypertension. Here we determined whether an increase in MBG is also implicated in age-associated arterial remodeling in DSS. Methods: Life span was measured in 60 S-D and 78 DSS. BP, pulse wave velocity (PWV), behavioral water maze test, ANGII, MBG and aortic collagen were assessed in 3 and 9-mo S-D and DSS on a normal 0.5% NaCl intake. Results: Median life span in DSS is reduced by 50% vs. S-D (12±1 vs. 24±2 mo, p<0.01). At 3-mo DSS had higher SBP, PWV, ANGII, MBG, aortic and large cerebral arterial wall remodeling vs. 3-mo S-D (Table). Between 3 and 9-mo DSS, but not S-D, exhibited further increase in SBP, PWV, MBG and aortic collagen deposition. In a redundant place-cue version of the water maze test, 3-mo DSS demonstrated numerically impaired spatial hippocampal memory vs. 3-mo S-D, and by 9-mo, performance in DSS suggested the development of motor impairments, thus precluding an uncontaminated assessment of their spatial memory. Conclusions: In DSS high MBG occurred concurrently with fibrosis of aorta and large cerebral arteries and numerically impaired spatial memory. With advancing age of DSS further increase in BP, aortic stiffness and spatial learning/motor deficit occurred in context with an increase in MBG, which suggested an implication of MBG in these declines.

Abstract P106: The Role of Inflammasomes and Angiotensin II Type 1 Receptor in the Pressor Responses of Aged Mice to Angiotensin II

Introduction: The prevalence of hypertension increases with age. Chronic low-grade inflammation commonly occurs with ageing, and inflammasomes are important initiators of inflammatory responses. We tested whether aged mice have enhanced pressor responses to angiotensin II (Ang II) and whether this is associated with exaggerated pro-inflammatory and vascular contractile responses. We also tested whether MCC950, a NLRP3 inflammasome inhibitor, reduces blood pressure (BP) in Ang II-treated aged mice. Methods: Young (8-12 weeks) and aged (24-30 months) male C57Bl6 mice were left untreated, or either treated with vehicle or a slow-pressor dose of Ang II (0.28 mg/kg/day) for 28 days. Another group of aged mice were treated with either Ang II + saline or Ang II + MCC950 (10 mg/kg/day) for 10 days. We measured systolic BP, mRNA expression of inflammatory markers and components of the renin-angiotensin system, and vascular contractile responses. Results: In young mice, Ang II caused a gradual increase in BP (final BP: 141.6 ± 8.3 mmHg), whereas BP increased by ~20 mmHg from baseline in aged mice, and continued to increase for 28 days (final BP: 155 ± 12.4 mmHg) (n=8-9, P<0.05). Ageing alone increased renal expression of AT1a receptors, NLRP3, Caspase-1, IL-1β, IL-33, CCR2, CCL7 and CCL8 by at least 1.5-fold (n=7-8, all P<0.05). Maximum contractile responses of mesenteric artery were 1.8-fold greater to Ang II and 1.2-fold greater to phenylephrine in aged vs young mice (n=4, both P<0.05). BP was not different between Ang II + saline-treated aged mice (BP: 138.8 ± 6.8 mmHg) and Ang II + MCC950-treated aged mice (BP: 144.7 ± 9.6 mmHg) (n=6-7, P>0.05). Conclusions: Aged mice have enhanced pressor responses to Ang II and this is associated with exacerbated pro-inflammatory and vascular contractile responses. The NLRP3 inflammasome does not appear to contribute to Ang II-induced hypertension in aged mice.

Family History of Hypertension and Arterial Elasticity Characteristics in Healthy Young People

Family history of hypertension is a primary predictor of high blood pressure (BP). This study attempted to determine whether there is a gradual increase in BP and an early change in arterial elasticity characteristics between young healthy individuals with or without a family history of hypertension and whether or not this increase is apparent in males as well as in females. A total of 270 normotensive healthy individuals (112 men and 158 women, aged 16 to 30 years) with or without a family history of hypertension, participated in conventional BP measurement and completed questionnaires covering basic information and a detailed family history of cardiovascular disease. Large arterial (capacitive) compliance (C1) and small arterial (oscillatory or reflective) compliance (C2) were derived from HDI/PulseWave CR-2000 (Hypertension Diagnostics, Minneapolis, USA). Based on family history information about parents and grandparents, three groups were formed: subjects with at least one hypertensive parent (group A), subjects with only hypertensive grandparents (group B), and subjects with normotensive parents and grandparents (group C). Men in group A had lower C1 and C2 along with higher systolic BP (SBP), diastolic BP (DBP), and heart rate than men in group C. Those in group B had intermediate C1, C2 and BP levels. C1 had a linear relationship with SBP, DBP, and heart rate. In the logistic regression model of family history of hypertension, C2 was lower in young normotensive males with parental hypertension (B = -0.315, exp B = 0.73, p = 0.03), independently of SBP, DBP, and heart rate. Among females, subjects with parental hypertension had higher systolic, mean arterial pressure, and pulse pressure (p < 0.05), and there were no significant differences in C1 and C2 between those with and those without parental hypertension. In conclusion, compared with normotensive offspring of normotensive parents, normotensive offspring of hypertensive parents had increased BP and impaired arterial properties, namely large and small arterial compliance as measured noninvasively by HDI. These differences were exhibited conspicuously in men but not in women. Alteration in arterial function in young non-hypertensive subjects may be a risk factor for hypertension and may contribute to the progression to hypertension later in life.

Ambulatory Blood Pressure and Family History of Hypertension in Healthy Men and Women

Family history of hypertension is a primary predictor of high blood pressure (BP). This study attempted to determine whether there is a gradual increase in BP between individuals with two hypertensive parents, one hypertensive parent, and normotensive parents and whether this increase is apparent with both ambulatory and casual BP assessments in men as well as in women. A total of 220 healthy men and women, aged 22 to 50 years, completed two 24-h ambulatory BP sessions (one work day and one off work day). Based on family history information obtained from parents, three groups were formed: subjects with two hypertensive parents, one hypertensive parent, and normotensive parents. Work and off work days did not differ; analyses were based on mean values of the 2 days. Men with two hypertensive parents had higher daytime and night-time ambulatory BP than men with normotensive parents. Those with one hypertensive parent had intermediate BP levels. Ambulatory BP was not associated with family history in women. Also, men with one or two hypertensive parents had higher ambulatory BP than women with hypertensive parents, whereas offspring of normotensive parents exhibited no sex differences in BP. Elevated systolic and diastolic BP throughout the day and night seems to characterize men with two hypertensive parents. In evaluating the relationship between family history of hypertension and BP, it is important to use ambulatory BP measures, differentiate between individuals with one and with two hypertensive parents, and focus on gender differences in BP.

Oral reduced B-nicotinamide adenine dinucleotide (NADH) affects blood pressure, lipid peroxidation, and lipid profile in hypertensive rats (SHR).

A gradual increase in blood pressure (BP), often attaining hypertensive levels, is common during aging--"age-related hypertension." Therefore, means to prevent or ameliorate this elevated BP safely are important. Although oral B-nicotinamide adenine dinucleotide (NADH), a natural coenzyme, is used principally to treat various neurologic disorders, we wished to investigate whether this agent had the same potential to lower BP and benefit the cardiovascular system as does coenzyme Q10, a similar-type agent. As a first approximation, spontaneously hypertensive rats (SHR) were used to determine effects of oral NADH. In a blinded, placebo-controlled study, ten rats received placebo; and ten, NADH for ten weeks. Systolic BP was measured by tail plethysmography. Blood was collected terminally, and chemistries were performed by routine methodologies. Thiobarbituric acid reactive species (TBARS) (an estimate of lipid peroxidation/free radical formation) was measured in renal and hepatic tissues. The following was noted: water and food intake were comparable, and the steady weight gain of young SHR were similar in the placebo and NADH groups. Although systolic BP did not differ between the two groups over the first month, it decreased and stayed markedly lower for the remainder of study in SHR receiving oral NADH. At the end of 60 days, SBP in NADH-treated SHR was 184 mm Hg +/- 2.8 (SEM) compared to 201 mm Hg +/- 2.1 (SEM) in control SHR (p < 0.001). No significant differences were seen in blood levels of glucose, insulin, triglyceride, and HDL levels but NADH intake lowered total cholesterol (p < 0.002) and LDL (p < 0.02). Renal TBARS were also significantly lower in SHR receiving NADH (P < 0.001). Accordingly, supplementation with the natural coenzyme NADH theoretically could prove to be useful in preventing age-related increases in BP and, thus, various cardiovascular maladies.

Hypertension inhibits noxious-evoked c-fos expression in the rat spinal cord.

The effect of hypertension on spinal induction of the c-fos proto-oncogene following noxious mechanical stimulation of the skin was studied in the rat. The occlusion of renal artery raised blood pressure steeply, reaching 52% over initial values. Oral administration of NG-nitro-L-arginine methyl ester provoked a gradual increase in blood pressure which reached up to 62%. The numbers of spinal dorsal horn Fos-immunoreactive nuclei were reduced to 66% and 38% of controls in animals with renal- and pharmacologically-induced hypertension, respectively. These data indicate that hypertension is accompanied by an inhibition of spinal nociceptive neurones which probably accounts for the hypoalgesia observed in hypertensive subjects. They further suggest an influence by the rate of increase of blood pressure on the level of spinal inhibition.

Angiotensin II Induces Cardiac Phenotypic Modulation and Remodeling In Vivo in Rats

Cardiac phenotypic modulation and remodeling appear to be involved in the pathophysiology of cardiac hypertrophy and heart failure. We undertook this study to examine whether angiotensin II (Ang II) in vivo, independent of blood pressure, contributes to cardiac phenotypic modulation and remodeling. A low dose (200 ng/kg per minute) of Ang II was continuously infused into rats by osmotic minipump for 24 hours or 3 or 7 days to examine the effects on the expression of cardiac phenotype-related or fibrosis-related genes. This Ang II dose caused a small and gradual increase in blood pressure over 7 days. Left ventricular mRNAs for skeletal alpha-actin, beta-myosin heavy chain, atrial natriuretic polypeptide, and fibronectin were already increased by 6.9-, 1.8-, 4.8-, and 1.5-fold, respectively, after 24 hours of Ang II infusion and by 6.9-, 3.3-, 7.5-, and 2.5-fold, respectively, after 3 days, whereas ventricular alpha-myosin heavy chain and smooth muscle alpha-actin mRNAs were not significantly altered by Ang II infusion. Ventricular transforming growth factor-beta 1 and types I and III collagen mRNA levels did not increase at 24 hours and began to increase by 1.4-, 2.8-, and 2.1-fold, respectively, at 3 days. An increase in left ventricular weight occurred 3 days after Ang II infusion. Treatment with TCV-116 (3 mg/kg per day), a nonpeptide selective angiotensin type 1 receptor antagonist, completely inhibited the above-mentioned Ang II-induced increases in ventricular gene expressions and weight. Hydralazine (10 mg/kg per day), which completely normalized blood pressure, did not block cardiac hypertrophy or increased cardiac gene expressions by Ang II.(ABSTRACT TRUNCATED AT 250 WORDS)

Is systemically administered oxytocin an analgesic in rats?

The effect of systemically administered oxytocin and a specific oxytocin antagonist, 1-deamino-2- d-Tyr(OEt)-4-Thr-8-Orn-oxytocin, on heat pain sensitivity was examined in rats. Intrapcritoneal (i.p.) oxytocin at 1 mg/kg, but not at 0.1 and 0.3 mg/kg, significantly increased response latencies on the hot-plate test. However, the rats displayed clear signs of sedation, motor impairment and vasoconstriction after 1 mg/kg oxytocin. Skin temperature on the plantar surface of the hind paws was also significantly decreased by this dose of oxytocin. The oxytocin antagonist (1 mg/kg i.p.) did not influence response latency. Since increased response latency was not the only behavioral effect of oxytocin, we conducted electrophysiological experiments to examine the effect of systemic oxytocin on the nociceptive flexor reflex in decerebrate, spinalized. unanesthetized rats. Oxytocin at 0.1 mg/kg i.p. did not influence flexor reflex magnitude, mean blood pressure or heart rate. Oxytocin at 0.3 and 1 mg/kg caused a gradual increase in blood pressure with stronger effect observed with 1 mg/kg. Neither 0.3 nor 1 mg/kg oxytocin significantly influenced the flexor reflex magnitude and heart rate. We thus conclude that systemic oxytocin did not produce analgesia in rats and the observed increase in response latency in the hot-plate test may result from the sedative and vasoconstrictive effects of this peptide. Furthermore, since the oxytocin antagonist did not significantly alter response latency on the hot-plate test, it is unlikely that endogenous oxytocin exerts a tonic effect on the pain threshold in rats.

Renal hemodynamics in canine DOCA-salt hypertension: effect of calcium channel blockade.

Systemic arterial blood pressure (BP), renal blood flow (RBF), and renal vascular resistance (RVR) were followed for 3-4 wks during the progression of DOCA-salt hypertension in the conscious dog. Accompanying the gradual increase in BP was an increase in RBF; however, RVR was unchanged. The hypertension was totally reversed 5-7 days after cessation of DOCA-salt treatment, but the increase in RBF persisted, presumably as a result of renal hypertrophy. Renal adrenoceptor blockade with prazosin (6 dogs) and prazosin plus idazoxan (4 dogs) caused a comparable decrease in BP in the normotensive and DOCA-salt hypertensive dog; however, RVR was decreased only in the normotensive. Similar results were obtained during ganglionic blockade with hexamethonium. The i.v. infusion of diltiazem for 1 wk restored BP of the hypertensive dog to a normotensive level, and hexamethonium given i.v. had little further effect on either BP or RVR. These results suggest a non-neurogenically mediated mechanism of canine DOCA-salt hypertension that is susceptible to calcium channel blockade.

The relationship between sexual maturity rating, age, and increased blood pressure in adolescents

Blood pressure values are known to vary with age and body size. The effect of sexual maturity was explored in 746 patients in an adolescent clinic. Systolic blood pressure for boys and girls showed an increase with a change from Tanner stage 2 to 3. Diastolic blood pressure did not increase. Both systolic and diastolic blood pressures showed a weight effect that was generally maintained within the Tanner stages. The gradual increase in blood pressure for large groups of adolescents would appear to be the result of the aggregate increase in size (weight) resulting from the asynchronous growth spurts of individuals studied. Consequently, those individuals with a strikingly early or late onset of maturation may have erroneous interpretations of their blood pressure. As biologic outliers, the borderline hypertensive who matures early may be overidentified, while the late maturer might go unrecognized.

The mechanism of disappearance of the physiologic third heart sound with age.

To study the mechanism of disappearance of the physiologic third heart sound (S3) with advancing age, combined phonoechocardiographic and phonomechanocardiographic recordings from 165 normal subjects between 6 and 62 years old were quantitatively analyzed. Nearly all individuals under 40 years old had a recordable S3. Although recordable in 38.6% of the 44 subjects over 40 years old, the physiologic S3 found in adults was less intense and occurred later in diastole when compared with that in children and adolescents. Marked changes in left ventricular filling hemodynamics were observed with aging, including an increase in left ventricular wall thickness and mass, a prolongation of the left ventricular isovolumetric relaxation period, a decrease in left ventricular early diastolic filling and wall thinning rates, and a reduction in the height and steepness of the rapid filling wave measured on the calibrated left apexcardiogram (linear correlation with age significant at p less than .001 for all parameters). Although less pronounced, these changes were very similar to the diastolic abnormalities found in patients with pressure overload left ventricular hypertrophy. Therefore, the higher pressure load imposed on the left ventricular wall due to the well-known gradual increase in blood pressure that occurs during normal growth and adulthood appears to be the most likely explanation for the observed changes in diastolic filling. It is concluded that the later occurrence, the diminishing amplitude, and the eventual complete disappearance of the physiologic S3 with age results from a decrease in early diastolic left ventricular filling and subsequent deceleration of inflow caused by the development of relative left ventricular hypertrophy in adulthood as compared with childhood.

Acute and long-term antihypertensive effect of bopindolol ? A nonselective ?-adrenergic blocker with ISA

14 male hypertensive patients, mean age 53 years first took part in a 3 month, double-blind crossover comparison of 1-2 mg bopindolol, a nonselective beta-blocker with ISA, and 100-200 mg metoprolol. Effects on blood pressure and heart rate were followed. One patient dropped out after the initial phase and the remaining 13 patients were followed for 1 year on bopindolol. 8 patients measured blood pressure at home, and in them bopindolol 1 mg o.d. and 8 mg once weekly were compared in a double-blind fashion, for 3 weeks on each regimen. Finally, after 1 year on bopindolol, treatment was withdrawn and blood pressure and heart rate were followed in 10 of the initial patients. Bopindolol in a mean dose of 1.35 mg/day caused a significant reduction in blood in pressure (26/15 mmHg), as did metoprolol (24/13 mmHg) in a mean dose of 144 mg/day. No significant difference in antihypertensive response was observed. Supine and standing heart rate were reduced both during bopindolol and metoprolol treatment. During long-term therapy with bopindolol, satisfactory blood pressure control was maintained up to 1 year in all patients, the average supine blood pressure being reduced from 173/107 to 144/90 mmHg. During treatment with bopindolol 8 mg once weekly, the blood pressure control was satisfactorily maintained over the week and no significant difference was observed in comparison with daily administration (1 mg) of the drug. When active treatment was withdrawn, a gradual increase in blood pressure and heart rate was observed, the pretreatment values being reached 8 weeks after discontinuation of bopindolol therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular effects of intraventricular injection of fmrfamide, met-enkephalin and their common analogues in the rat

1. The molluscan neuropeptide, Phe-Met-Arg-Phe-NH 2 (FMRFamide), the mammalian opioid peptide met-enkephalin, and their common analogues, met-enkephalin-Arg 6-Phe 7 (YGGFMRF) and Tyr-Gly-Gly-Phe-Met-Arg-Phe-amide (YGGFMRFamide), were injected into the lateral ventricle of the rat; the cardiovascular effects were studied. 2. FMRFamide caused a rapid, transient elevation in blood pressure accompanied by a great increase in pulse pressure. These effects were followed by secondary increases in blood and pulse pressures. 3. Met-enkephalin produced an initial reduction in blood pressure which was followed by a gradual increase at the higher of two test doses (300 nmole). 4. Injection of YGGFMRF resulted in a gradual increase in blood pressure. This response resembled that to met-enkephalin. 5. The initial response to YGGFMRFamide was similar to that to FMRFamide: increases in both blood and pulse pressures after injection. However, the secondary effect of YGGFMRFamide, a prolonged reduction in blood pressure, was not produced by FMRFamide. These results suggest that the initial excitatory cardiovascular responses may be due to the presence of the C-terminal amide. 6. All of the cardiovascular effects of injecting these peptides into the lateral ventricle were abolished by pre-treatment with naloxone in a dose that, itself, produced no cardiovascular changes. In conclusion, these peptides seem to act via the naloxone sensitive opiate receptors in the rat brain.

Methodology of Blood Pressure Measurements

The most used parameters to measure fetal outcome are the perinatal mortality and morbidity. The perinatal mortality rises if the systolic and diastolic blood pressures exceed 140 and 90 mmHg, respectively, or when the systolic blood pressure is lower than 105 mmHg. The found dividing line of 140/90 mmHg is however not strict, because a gradual increase in blood pressure shows also a gradual rise in perinatal mortality.1 The data from the Collaborative Perinatal Project suggest that this mortality rises abruptly, if the diastolic blood pressure exceeds 84 mmHg.2